Leptin
Receptors, Leptin
Obesity
Hypothalamus
Adipose Tissue
Mice, Obese
Body Weight
Insulin
Receptors, Cell Surface
Adiponectin
Arcuate Nucleus
Proteins
STAT3 Transcription Factor
Ghrelin
Energy Metabolism
Pro-Opiomelanocortin
Neuropeptide Y
Body Mass Index
Adipokines
Adipocytes
Agouti-Related Protein
RNA, Messenger
Anorexia
Adiposity
Signal Transduction
Mice, Inbred C57BL
Rats, Zucker
Peptide Hormones
Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. (1/1089)
Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels. Here we examine pancreatic islets isolated from pancreata of human donors for their responses to leptin. The presence of leptin receptors on islet beta-cells was demonstrated by double fluorescence confocal microscopy after binding of a fluorescent derivative of human leptin (Cy3-leptin). Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose. Intracellular calcium responses to 16.7 mM glucose were rapidly reduced by leptin. Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose. Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose. These findings demonstrate direct suppressive effects of leptin on insulin-producing beta-cells in human islets at the levels of both stimulus-secretion coupling and gene expression. The findings also further indicate the existence of an adipoinsular axis in humans in which insulin stimulates leptin production in adipocytes and leptin inhibits the production of insulin in beta-cells. We suggest that dysregulation of the adipoinsular axis in obese individuals due to defective leptin reception by beta-cells may result in chronic hyperinsulinemia and may contribute to the pathogenesis of adipogenic diabetes. (+info)Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. (2/1089)
The receptor for the gene product of the obesity gene, leptin, was recently reported to be expressed on murine and human hematopoietic progenitor cells. Therefore, we studied the expression of the leptin receptor, OB-R, in normal myeloid precursors, human leukemia cell lines, and primary leukemic cells using reverse-transcriptase polymerase chain reaction. In normal hematopoiesis, OB-R was expressed in CD34(+) cells. Normal promyelocytes (CD34(-)33(+) and CD34(-)13(+)) expressed only very low levels of the short, presumably nonsignaling isoform. Both the long and short isoforms of OB-R were expressed in 10 of 22 samples from patients with newly diagnosed primary or secondary acute myeloid leukemia (AML), with a higher incidence of the long isoform in primary AML (87.6% v 28.6%; P =.01). The incidence of OB-R expression was higher in recurrent than in newly diagnosed AML (P <.001), and samples from four patients with refractory AML showed strong expression of both isoforms. Both OB-R isoforms were also expressed in newly diagnosed and recurrent acute promyelocytic leukemia cells but were essentially absent in samples of chronic or acute lymphocytic leukemia. In vitro growth of myeloid leukemic cell lines and of blasts from 14 primary AMLs demonstrated that recombinant human leptin alone induced low level proliferation, significantly (P <.05) increased proliferation induced by recombinant human granulocyte colony-stimulating factor, interleukin 3, and stem cell factor in a subset of AML and increased colony formation (P <.005). Also, leptin reduced apoptosis induced by cytokine withdrawal in MO7E and TF-1 cells. Serum leptin levels correlated only with body mass index (P <. 001) and gender (P =.03). Results confirm the reported expression of leptin receptor in normal CD34(+) cells and demonstrate the frequent expression of leptin receptors in AML blasts. While normal promyelocytes lack receptor expression, leukemic promyelocytes express both isoforms. We also demonstrate proliferative effects of leptin alone and in combination with other physiologic cytokines, and anti-apoptotic properties of leptin. These findings could have implications for the pathophysiology of AML. (+info)The role of the sympathetic nervous system in the regulation of leptin synthesis in C57BL/6 mice. (3/1089)
The objectives of this study were to determine whether leptin synthesis is regulated by the sympathetic nervous system and if so whether beta-adrenergic receptors mediate this effect. We show that sympathetic blockade by reserpine increases leptin mRNA levels in brown but not white adipose tissue, while acute cold-exposure decreases leptin expression 10-fold in brown adipose tissue and 2-fold in white adipose tissue. The cold-induced reduction in leptin mRNA can be prevented by a combination of propranolol and SR 59230A but not by either antagonist alone, indicating that beta3-adrenergic receptors and classical beta1/beta2-adrenergic receptors both mediate responses to sympathetic stimulation. Circulating leptin levels reflect synthesis in white adipose tissue but not in brown adipose tissue. (+info)Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. (4/1089)
The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus. To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor (Ob-Rb). Thus, mRNAs encoding NPY and pro-opiomelanocortin (POMC) were colocalized in the arcuate nucleus of fed and fasted rats by fluorescence in situ hybridization in combination with isotopic in situ hybridization for Ob-Rb mRNA. In fed animals, 47% of arcuate nucleus neurons containing NPY mRNA also contained Ob-Rb mRNA, compared with 79% of POMC neurons (P < 0.01). After a 2-day fast, the number of arcuate nucleus neurons with NPY mRNA increased 50% (P < 0.05); the number of these that coexpressed Ob-Rb increased twofold (P = 0.013). Furthermore, Ob-Rb mRNA hybridization in individual NPY neurons increased by 64% (P < 0.02). In contrast, the number of POMC neurons that coexpressed Ob-Rb was unchanged. A significant interpretation of these findings is that the NPY neurons that do not express detectable levels of Ob-Rb mRNA are not activated by fasting, whereas the NPY neurons that are activated by fasting are the ones that express Ob-Rb. These data demonstrate a significant physiological difference between NPY neurons that express Ob-Rb and those that do not. The results support the conclusion that the effect of food intake on NPY neurons is mediated by the direct action of leptin via Ob-Rb receptors expressed by these NPY cells. The results also indicate that expression of Ob-Rb is a defining phenotypic characteristic of the subset of arcuate nucleus NPY neurons that are activated by fasting and play a central role in the adaptive response to negative energy balance. (+info)Leptin responsiveness and gene dosage for leptin receptor mutation (fa) in newborn rats. (5/1089)
To determine the degree to which the leptin receptor mutation (fa) influences the responsiveness to leptin during the first postnatal week, we injected recombinant leptin (600 pmol. g-1. day-1 sc from day 1 to day 7) into wild-type (+/+), heterozygous (+/fa), and fatty (fa/fa) rat pups. Growth and final body fat content of these leptin-treated pups were compared with those of saline-treated littermates of the same genotype. The body mass of the leptin-treated +/+ pups, but not that of the +/fa and fa/fa pups, increased more slowly than that of their respective controls, and fat content at day 7 was reduced by 37% in +/+ pups, by 22% in +/fa pups, but not at all in fa/fa pups. Plasma leptin remained excessively high throughout the day under this treatment, but a 30-fold lower leptin dose, causing only moderate changes of plasma leptin, still reduced the body fat of +/+ pups significantly. We conclude that leptin participates in the control of even the earliest stages of fat deposition and that the response to supraphysiological doses of leptin is markedly reduced in 1-wk-old pups with one fa allele and absent in pups with two fa alleles. (+info)Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice. (6/1089)
During gestation, heterozygous C57BLKS/J-Lepr(db/+) mice develop spontaneous gestational diabetes mellitus (GDM), and the newborn fetuses are macrosomic compared with offspring from wild-type (+/+) mothers. To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy, we studied +/+, db/+, and db/+ transgenic mice that overexpress the human GLUT4 gene two- to three-fold (db/+TG6). During pregnancy, fasting plasma glucose and hepatic glucose production were twofold greater in db/+ than +/+ mice, despite similar insulin levels. In skeletal muscle, insulin-stimulated tyrosine phosphorylation was decreased in pregnant +/+ mice, and even more so in db/+ mice: insulin receptor beta (IR-beta), +/+ 34%, db/+ 57% decrease, P<0.05; insulin receptor substrate 1 (IRS-1), +/+ 44%, db/+ 61% decrease, P<0.05; and phosphoinositol (PI) 3-kinase (p85alpha), +/+ 33%, db/+ 65% decrease, P<0.05. Overexpression of GLUT4 in db/+TG6 mice markedly improved glucose-stimulated insulin secretion, by 250%, and increased IRbeta, IRS-1, and p85alpha phosphorylation twofold, despite no change in concentration of these proteins. Plasma leptin concentration increased 40-fold during pregnancy, from 2.2+/-0.5 to 92+/-11 ng/ml and 3.6+/-0.1 to 178+/-34 ng/ml in +/+ and db/+ mice, respectively (P<0.01), but was increased to only 23+/-3 ng/ml in pregnant db/+TG6 mice (P<0.001). Maternal fat mass and energy intake were greater in db/+ mice, and fat mass was reduced by GLUT4 overexpression, independent of food intake. Fetal body weight was increased by 8.1 and 7.9% in db/+ and db/+TG6 mothers, respectively (P<0.05), regardless of fetal genotype, whereas fetuses from db/+TG8 mothers (four- to fivefold overexpression) weighed significantly less compared with pups from +/+ or db/+ mothers (P<0.05). These results suggest that the single mutant db allele effects susceptibility to GDM through abnormalities in insulin receptor signaling, defective insulin secretion, and greater nutrient availability. GLUT4 overexpression markedly improves insulin-signaling in GDM, resulting in increased insulin secretion and improved glycemic control. However, maternal hyperglycemia appears not to be the sole cause of fetal macrosomia. These data suggest that GDM is associated with defects in insulin receptor signaling in maternal skeletal muscle, and this may be an important factor provoking maternal and fetal perinatal complications. (+info)Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downregulation. (7/1089)
Long (ObRb) and short (ObRa) leptin receptor isoforms are thought to play essential roles in mediating leptin signaling and the transport and degradation of leptin, respectively. Although the capacity of these cloned receptor species to mediate signal transduction has been reported, there is no information on the ability of individual receptor species to mediate leptin internalization and degradation or to undergo ligand-induced downregulation. We therefore studied these parameters in Chinese hamster ovary (CHO) cells stably expressing either ObRa or ObRb isoforms of the leptin receptor. We determined that both ObRa and ObRb mediated internalization of 125I-labeled leptin by a temperature- and coated pit-dependent mechanism. Both ObRa and ObRb also mediated degradation of 125I-leptin by a lysosomal mechanism, and this was more efficiently mediated by ObRa in these cells. Neither leptin internalization nor degradation by ObRa was affected by mutation of the conserved Box 1 motif. By studying deletion mutants of ObRa, we found that efficient internalization was dependent on a motif located between amino acids 8 and 29 of the intracellular domain of ObRa. Exposure of cells expressing ObRa or ObRb to unlabeled leptin for 90 min at 37 degrees C produced downregulation of available surface receptors, and this effect was of greater magnitude in cells expressing ObRb. Whereas CHO cells expressing the growth hormone receptor showed marked downregulation of ligand binding after exposure to dexamethasone (DEX) or phorbol myristic acid (PMA), PMA had no effect on expression of ObRa or ObRb, and DEX reduced binding to cells expressing ObRb by 15%. Thus, the two leptin receptor isoforms, ObRa and ObRb, mediate leptin internalization by a coated pit-dependent mechanism, leptin degradation by a lysosomal pathway, and ligand-induced receptor downregulation. The differential capacity of the two receptor isoforms may relate to the different roles of the receptor isoforms in the biology of leptin. (+info)Leptin promotes aggregation of human platelets via the long form of its receptor. (8/1089)
Plasma leptin levels are elevated in most obese individuals, and obesity is accompanied by a high incidence of cardiovascular disease. Therefore, leptin could be involved in the pathogenesis of cardiovascular disease. In the present study, the role of leptin was explored in the regulation of platelet function. The expression of the long form of the leptin receptor was detected in human platelets. At 50 ng/ml, human leptin induced phosphorylation of several proteins of platelets at the tyrosine residue. Neither leptin at concentrations < or = 100 ng/ml nor ADP at concentrations > or = 1 micromol/l affected platelet aggregation. However, after pretreatment with 100 ng/ml leptin for 5 min, 1 micromol/l ADP caused aggregation. Thus, leptin and ADP acted synergistically. At a concentration of 2 micromol/l, ADP induced platelet aggregation, which was markedly enhanced by 30-100 ng/ml leptin in a concentration-dependent manner. This concentration range corresponds to that of plasma leptin levels in obese individuals. At the lower concentrations (< 10 ng/ml) that are observed in normal individuals, leptin had no effect on platelet aggregation. In conclusion, leptin at high concentrations has the novel function of promoting platelet aggregation, which may be a key coupling factor between obesity and the cardiovascular disease associated with syndrome X and diabetes. (+info)Leptin is a hormone primarily produced and released by adipocytes, which are the fat cells in our body. It plays a crucial role in regulating energy balance and appetite by sending signals to the brain when the body has had enough food. This helps control body weight by suppressing hunger and increasing energy expenditure. Leptin also influences various metabolic processes, including glucose homeostasis, neuroendocrine function, and immune response. Defects in leptin signaling can lead to obesity and other metabolic disorders.
Leptin receptors are cell surface receptors that bind to and respond to the hormone leptin. These receptors are found in various tissues throughout the body, including the hypothalamus in the brain, which plays a crucial role in regulating energy balance and appetite. Leptin is a hormone produced by adipose (fat) tissue that signals information about the size of fat stores to the brain. When leptin binds to its receptors, it activates signaling pathways that help regulate energy intake and expenditure, body weight, and glucose metabolism.
There are several subtypes of leptin receptors (LEPR), including LEPRa, LEPRb, LEPC, and LEPD. Among these, the LEPRb isoform is the most widely expressed and functionally important form. Mutations in the gene encoding the leptin receptor can lead to obesity, hyperphagia (excessive hunger), and impaired energy metabolism, highlighting the importance of this receptor in maintaining energy balance and overall health.
Obesity is a complex disease characterized by an excess accumulation of body fat to the extent that it negatively impacts health. It's typically defined using Body Mass Index (BMI), a measure calculated from a person's weight and height. A BMI of 30 or higher is indicative of obesity. However, it's important to note that while BMI can be a useful tool for identifying obesity in populations, it does not directly measure body fat and may not accurately reflect health status in individuals. Other factors such as waist circumference, blood pressure, cholesterol levels, and blood sugar levels should also be considered when assessing health risks associated with weight.
The hypothalamus is a small, vital region of the brain that lies just below the thalamus and forms part of the limbic system. It plays a crucial role in many important functions including:
1. Regulation of body temperature, hunger, thirst, fatigue, sleep, and circadian rhythms.
2. Production and regulation of hormones through its connection with the pituitary gland (the hypophysis). It controls the release of various hormones by producing releasing and inhibiting factors that regulate the anterior pituitary's function.
3. Emotional responses, behavior, and memory formation through its connections with the limbic system structures like the amygdala and hippocampus.
4. Autonomic nervous system regulation, which controls involuntary physiological functions such as heart rate, blood pressure, and digestion.
5. Regulation of the immune system by interacting with the autonomic nervous system.
Damage to the hypothalamus can lead to various disorders like diabetes insipidus, growth hormone deficiency, altered temperature regulation, sleep disturbances, and emotional or behavioral changes.
The medical definition of "eating" refers to the process of consuming and ingesting food or nutrients into the body. This process typically involves several steps, including:
1. Food preparation: This may involve cleaning, chopping, cooking, or combining ingredients to make them ready for consumption.
2. Ingestion: The act of taking food or nutrients into the mouth and swallowing it.
3. Digestion: Once food is ingested, it travels down the esophagus and enters the stomach, where it is broken down by enzymes and acids to facilitate absorption of nutrients.
4. Absorption: Nutrients are absorbed through the walls of the small intestine and transported to cells throughout the body for use as energy or building blocks for growth and repair.
5. Elimination: Undigested food and waste products are eliminated from the body through the large intestine (colon) and rectum.
Eating is an essential function that provides the body with the nutrients it needs to maintain health, grow, and repair itself. Disorders of eating, such as anorexia nervosa or bulimia nervosa, can have serious consequences for physical and mental health.
Adipose tissue, also known as fatty tissue, is a type of connective tissue that is composed mainly of adipocytes (fat cells). It is found throughout the body, but is particularly abundant in the abdominal cavity, beneath the skin, and around organs such as the heart and kidneys.
Adipose tissue serves several important functions in the body. One of its primary roles is to store energy in the form of fat, which can be mobilized and used as an energy source during periods of fasting or exercise. Adipose tissue also provides insulation and cushioning for the body, and produces hormones that help regulate metabolism, appetite, and reproductive function.
There are two main types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is the more common form and is responsible for storing energy as fat. BAT, on the other hand, contains a higher number of mitochondria and is involved in heat production and energy expenditure.
Excessive accumulation of adipose tissue can lead to obesity, which is associated with an increased risk of various health problems such as diabetes, heart disease, and certain types of cancer.
I cannot precisely define "obese mice" from a medical perspective because "obesity" is typically defined for humans and companion animals based on body weight relative to body size. However, I can provide you with relevant information regarding obese mice in a research or laboratory context.
Obesity in mice is often induced by providing them with a high-fat diet (HFD) to promote excessive weight gain and metabolic dysfunction. This allows researchers to study the effects of obesity on various health parameters, such as insulin resistance, inflammation, and cardiovascular function.
In laboratory settings, mice are often considered obese if their body weight is 10-20% higher than the average for their strain, age, and sex. Researchers also use body mass index (BMI) or body fat percentage to determine obesity in mice. For example:
* Body Mass Index (BMI): Mice with a BMI greater than 0.69 g/cm² are considered obese. To calculate BMI, divide the body weight in grams by the square of the nose-to-anus length in centimeters.
* Body Fat Percentage: Obesity can also be determined based on body fat percentage using non-invasive methods like magnetic resonance imaging (MRI) or computed tomography (CT) scans. Mice with more than 45% body fat are generally considered obese.
It is important to note that these thresholds may vary depending on the mouse strain, age, and sex. Researchers should consult relevant literature for their specific experimental setup when defining obesity in mice.
Body weight is the measure of the force exerted on a scale or balance by an object's mass, most commonly expressed in units such as pounds (lb) or kilograms (kg). In the context of medical definitions, body weight typically refers to an individual's total weight, which includes their skeletal muscle, fat, organs, and bodily fluids.
Healthcare professionals often use body weight as a basic indicator of overall health status, as it can provide insights into various aspects of a person's health, such as nutritional status, metabolic function, and risk factors for certain diseases. For example, being significantly underweight or overweight can increase the risk of developing conditions like malnutrition, diabetes, heart disease, and certain types of cancer.
It is important to note that body weight alone may not provide a complete picture of an individual's health, as it does not account for factors such as muscle mass, bone density, or body composition. Therefore, healthcare professionals often use additional measures, such as body mass index (BMI), waist circumference, and blood tests, to assess overall health status more comprehensively.
Insulin is a hormone produced by the beta cells of the pancreatic islets, primarily in response to elevated levels of glucose in the circulating blood. It plays a crucial role in regulating blood glucose levels and facilitating the uptake and utilization of glucose by peripheral tissues, such as muscle and adipose tissue, for energy production and storage. Insulin also inhibits glucose production in the liver and promotes the storage of excess glucose as glycogen or triglycerides.
Deficiency in insulin secretion or action leads to impaired glucose regulation and can result in conditions such as diabetes mellitus, characterized by chronic hyperglycemia and associated complications. Exogenous insulin is used as a replacement therapy in individuals with diabetes to help manage their blood glucose levels and prevent long-term complications.
Cell surface receptors, also known as membrane receptors, are proteins located on the cell membrane that bind to specific molecules outside the cell, known as ligands. These receptors play a crucial role in signal transduction, which is the process of converting an extracellular signal into an intracellular response.
Cell surface receptors can be classified into several categories based on their structure and mechanism of action, including:
1. Ion channel receptors: These receptors contain a pore that opens to allow ions to flow across the cell membrane when they bind to their ligands. This ion flux can directly activate or inhibit various cellular processes.
2. G protein-coupled receptors (GPCRs): These receptors consist of seven transmembrane domains and are associated with heterotrimeric G proteins that modulate intracellular signaling pathways upon ligand binding.
3. Enzyme-linked receptors: These receptors possess an intrinsic enzymatic activity or are linked to an enzyme, which becomes activated when the receptor binds to its ligand. This activation can lead to the initiation of various signaling cascades within the cell.
4. Receptor tyrosine kinases (RTKs): These receptors contain intracellular tyrosine kinase domains that become activated upon ligand binding, leading to the phosphorylation and activation of downstream signaling molecules.
5. Integrins: These receptors are transmembrane proteins that mediate cell-cell or cell-matrix interactions by binding to extracellular matrix proteins or counter-receptors on adjacent cells. They play essential roles in cell adhesion, migration, and survival.
Cell surface receptors are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and cell growth and differentiation. Dysregulation of these receptors can contribute to the development of numerous diseases, such as cancer, diabetes, and neurological disorders.
Adiponectin is a hormone that is produced and secreted by adipose tissue, which is another name for body fat. This hormone plays an important role in regulating metabolism and energy homeostasis. It helps to regulate glucose levels, break down fatty acids, and has anti-inflammatory effects.
Adiponectin is unique because it is exclusively produced by adipose tissue, and its levels are inversely related to body fat mass. This means that lean individuals tend to have higher levels of adiponectin than obese individuals. Low levels of adiponectin have been associated with an increased risk of developing various metabolic disorders, such as insulin resistance, type 2 diabetes, and cardiovascular disease.
Overall, adiponectin is an important hormone that plays a crucial role in maintaining metabolic health, and its levels may serve as a useful biomarker for assessing metabolic risk.
The arcuate nucleus is a part of the hypothalamus in the brain. It is involved in the regulation of various physiological functions, including appetite, satiety, and reproductive hormones. The arcuate nucleus contains two main types of neurons: those that produce neuropeptide Y and agouti-related protein, which stimulate feeding and reduce energy expenditure; and those that produce pro-opiomelanocortin and cocaine-and-amphetamine-regulated transcript, which suppress appetite and increase energy expenditure. These neurons communicate with other parts of the brain to help maintain energy balance and reproductive function.
Proteins are complex, large molecules that play critical roles in the body's functions. They are made up of amino acids, which are organic compounds that are the building blocks of proteins. Proteins are required for the structure, function, and regulation of the body's tissues and organs. They are essential for the growth, repair, and maintenance of body tissues, and they play a crucial role in many biological processes, including metabolism, immune response, and cellular signaling. Proteins can be classified into different types based on their structure and function, such as enzymes, hormones, antibodies, and structural proteins. They are found in various foods, especially animal-derived products like meat, dairy, and eggs, as well as plant-based sources like beans, nuts, and grains.
STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor protein that plays a crucial role in signal transduction and gene regulation. It is activated through phosphorylation by various cytokines and growth factors, which leads to its dimerization, nuclear translocation, and binding to specific DNA sequences. Once bound to the DNA, STAT3 regulates the expression of target genes involved in various cellular processes such as proliferation, differentiation, survival, and angiogenesis. Dysregulation of STAT3 has been implicated in several diseases, including cancer, autoimmune disorders, and inflammatory conditions.
Ghrelin is a hormone primarily produced and released by the stomach with some production in the small intestine, pancreas, and brain. It is often referred to as the "hunger hormone" because it stimulates appetite, promotes food intake, and contributes to the regulation of energy balance.
Ghrelin levels increase before meals and decrease after eating. In addition to its role in regulating appetite and meal initiation, ghrelin also has other functions, such as modulating glucose metabolism, insulin secretion, gastric motility, and cardiovascular function. Its receptor, the growth hormone secretagogue receptor (GHS-R), is found in various tissues throughout the body, indicating its wide range of physiological roles.
Energy metabolism is the process by which living organisms produce and consume energy to maintain life. It involves a series of chemical reactions that convert nutrients from food, such as carbohydrates, fats, and proteins, into energy in the form of adenosine triphosphate (ATP).
The process of energy metabolism can be divided into two main categories: catabolism and anabolism. Catabolism is the breakdown of nutrients to release energy, while anabolism is the synthesis of complex molecules from simpler ones using energy.
There are three main stages of energy metabolism: glycolysis, the citric acid cycle (also known as the Krebs cycle), and oxidative phosphorylation. Glycolysis occurs in the cytoplasm of the cell and involves the breakdown of glucose into pyruvate, producing a small amount of ATP and nicotinamide adenine dinucleotide (NADH). The citric acid cycle takes place in the mitochondria and involves the further breakdown of pyruvate to produce more ATP, NADH, and carbon dioxide. Oxidative phosphorylation is the final stage of energy metabolism and occurs in the inner mitochondrial membrane. It involves the transfer of electrons from NADH and other electron carriers to oxygen, which generates a proton gradient across the membrane. This gradient drives the synthesis of ATP, producing the majority of the cell's energy.
Overall, energy metabolism is a complex and essential process that allows organisms to grow, reproduce, and maintain their bodily functions. Disruptions in energy metabolism can lead to various diseases, including diabetes, obesity, and neurodegenerative disorders.
Pro-opiomelanocortin (POMC) is a precursor protein that gets cleaved into several biologically active peptides in the body. These peptides include adrenocorticotropic hormone (ACTH), beta-lipotropin, and multiple opioid peptides such as beta-endorphin, met-enkephalin, and leu-enkephalin.
ACTH stimulates the release of cortisol from the adrenal gland, while beta-lipotropin has various metabolic functions. The opioid peptides derived from POMC have pain-relieving (analgesic) and rewarding effects in the brain. Dysregulation of the POMC system has been implicated in several medical conditions, including obesity, addiction, and certain types of hormone deficiencies.
Fasting is defined in medical terms as the abstinence from food or drink for a period of time. This practice is often recommended before certain medical tests or procedures, as it helps to ensure that the results are not affected by recent eating or drinking.
In some cases, fasting may also be used as a therapeutic intervention, such as in the management of seizures or other neurological conditions. Fasting can help to lower blood sugar and insulin levels, which can have a variety of health benefits. However, it is important to note that prolonged fasting can also have negative effects on the body, including malnutrition, dehydration, and electrolyte imbalances.
Fasting is also a spiritual practice in many religions, including Christianity, Islam, Buddhism, and Hinduism. In these contexts, fasting is often seen as a way to purify the mind and body, to focus on spiritual practices, or to express devotion or mourning.
Neuropeptide Y (NPY) is a neurotransmitter and neuropeptide that is widely distributed in the central and peripheral nervous systems. It is a member of the pancreatic polypeptide family, which includes peptide YY and pancreatic polypeptide. NPY plays important roles in various physiological functions such as energy balance, feeding behavior, stress response, anxiety, memory, and cardiovascular regulation. It is involved in the modulation of neurotransmitter release, synaptic plasticity, and neural development. NPY is synthesized from a larger precursor protein called prepro-NPY, which is post-translationally processed to generate the mature NPY peptide. The NPY system has been implicated in various pathological conditions such as obesity, depression, anxiety disorders, hypertension, and drug addiction.
Body Mass Index (BMI) is a measure used to assess whether a person has a healthy weight for their height. It's calculated by dividing a person's weight in kilograms by the square of their height in meters. Here is the medical definition:
Body Mass Index (BMI) = weight(kg) / [height(m)]^2
According to the World Health Organization, BMI categories are defined as follows:
* Less than 18.5: Underweight
* 18.5-24.9: Normal or healthy weight
* 25.0-29.9: Overweight
* 30.0 and above: Obese
It is important to note that while BMI can be a useful tool for identifying weight issues in populations, it does have limitations when applied to individuals. For example, it may not accurately reflect body fat distribution or muscle mass, which can affect health risks associated with excess weight. Therefore, BMI should be used as one of several factors when evaluating an individual's health status and risk for chronic diseases.
Adipokines are hormones and signaling molecules produced by adipose tissue, which is composed of adipocytes (fat cells) and stromal vascular fraction (SVF) that includes preadipocytes, fibroblasts, immune cells, and endothelial cells. Adipokines play crucial roles in various biological processes such as energy metabolism, insulin sensitivity, inflammation, immunity, angiogenesis, and neuroendocrine regulation.
Some well-known adipokines include:
1. Leptin - regulates appetite, energy expenditure, and glucose homeostasis
2. Adiponectin - improves insulin sensitivity, reduces inflammation, and has anti-atherogenic properties
3. Resistin - impairs insulin sensitivity and is associated with obesity and type 2 diabetes
4. Tumor necrosis factor-alpha (TNF-α) - contributes to chronic low-grade inflammation in obesity, insulin resistance, and metabolic dysfunction
5. Interleukin-6 (IL-6) - involved in the regulation of energy metabolism, immune response, and inflammation
6. Plasminogen activator inhibitor-1 (PAI-1) - associated with cardiovascular risk by impairing fibrinolysis and promoting thrombosis
7. Visfatin - has insulin-mimetic properties and contributes to inflammation and insulin resistance
8. Chemerin - regulates adipogenesis, energy metabolism, and immune response
9. Apelin - involved in the regulation of energy homeostasis, cardiovascular function, and fluid balance
10. Omentin - improves insulin sensitivity and has anti-inflammatory properties
The dysregulation of adipokine production and secretion is associated with various pathological conditions such as obesity, type 2 diabetes, metabolic syndrome, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD), cancer, and neurodegenerative disorders.
Intraventricular injections are a type of medical procedure where medication is administered directly into the cerebral ventricles of the brain. The cerebral ventricles are fluid-filled spaces within the brain that contain cerebrospinal fluid (CSF). This procedure is typically used to deliver drugs that target conditions affecting the central nervous system, such as infections or tumors.
Intraventricular injections are usually performed using a thin, hollow needle that is inserted through a small hole drilled into the skull. The medication is then injected directly into the ventricles, allowing it to circulate throughout the CSF and reach the brain tissue more efficiently than other routes of administration.
This type of injection is typically reserved for situations where other methods of drug delivery are not effective or feasible. It carries a higher risk of complications, such as bleeding, infection, or damage to surrounding tissues, compared to other routes of administration. Therefore, it is usually performed by trained medical professionals in a controlled clinical setting.
Blood glucose, also known as blood sugar, is the concentration of glucose in the blood. Glucose is a simple sugar that serves as the main source of energy for the body's cells. It is carried to each cell through the bloodstream and is absorbed into the cells with the help of insulin, a hormone produced by the pancreas.
The normal range for blood glucose levels in humans is typically between 70 and 130 milligrams per deciliter (mg/dL) when fasting, and less than 180 mg/dL after meals. Levels that are consistently higher than this may indicate diabetes or other metabolic disorders.
Blood glucose levels can be measured through a variety of methods, including fingerstick blood tests, continuous glucose monitoring systems, and laboratory tests. Regular monitoring of blood glucose levels is important for people with diabetes to help manage their condition and prevent complications.
Adipocytes are specialized cells that comprise adipose tissue, also known as fat tissue. They are responsible for storing energy in the form of lipids, particularly triglycerides, and releasing energy when needed through a process called lipolysis. There are two main types of adipocytes: white adipocytes and brown adipocytes. White adipocytes primarily store energy, while brown adipocytes dissipate energy as heat through the action of uncoupling protein 1 (UCP1).
In addition to their role in energy metabolism, adipocytes also secrete various hormones and signaling molecules that contribute to whole-body homeostasis. These include leptin, adiponectin, resistin, and inflammatory cytokines. Dysregulation of adipocyte function has been implicated in the development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease.
Agouti-related protein (AGRP) is a neuropeptide that functions as an endogenous antagonist of melanocortin receptors, specifically MC3R and MC4R. It is expressed in the hypothalamus and plays a crucial role in regulating energy balance, body weight, and glucose homeostasis. AGRP increases food intake and decreases energy expenditure by inhibiting melanocortin signaling in the hypothalamus. Dysregulation of AGRP has been implicated in various metabolic disorders, including obesity and type 2 diabetes.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
Anorexia is a medical condition defined as a loss of appetite or aversion to food, leading to significant weight loss. It can be a symptom of various underlying causes, such as mental health disorders (most commonly an eating disorder called anorexia nervosa), gastrointestinal issues, cancer, infections, or side effects of medication. In this definition, we are primarily referring to anorexia as a symptom rather than the specific eating disorder anorexia nervosa.
Anorexia nervosa is a psychological eating disorder characterized by:
1. Restriction of energy intake leading to significantly low body weight (in context of age, sex, developmental trajectory, and physical health)
2. Intense fear of gaining weight or becoming fat, or persistent behavior that interferes with weight gain
3. Disturbed body image, such as overvaluation of self-worth regarding shape or weight, or denial of the seriousness of low body weight
Anorexia nervosa has two subtypes: restricting type and binge eating/purging type. The restricting type involves limiting food intake without engaging in binge eating or purging behaviors (such as self-induced vomiting or misuse of laxatives, diuretics, or enemas). In contrast, the binge eating/purging type includes recurrent episodes of binge eating and compensatory behaviors to prevent weight gain.
It is essential to differentiate between anorexia as a symptom and anorexia nervosa as a distinct psychological disorder when discussing medical definitions.
"Adiposity" is a medical term that refers to the condition of having an excessive amount of fat in the body. It is often used to describe obesity or being significantly overweight. Adipose tissue, which is the technical name for body fat, is important for many bodily functions, such as storing energy and insulating the body. However, an excess of adipose tissue can lead to a range of health problems, including heart disease, diabetes, and certain types of cancer.
There are different ways to measure adiposity, including body mass index (BMI), waist circumference, and skinfold thickness. BMI is the most commonly used method and is calculated by dividing a person's weight in kilograms by their height in meters squared. A BMI of 30 or higher is considered obese, while a BMI between 25 and 29.9 is considered overweight. However, it's important to note that BMI may not accurately reflect adiposity in some individuals, such as those with a lot of muscle mass.
In summary, adiposity refers to the condition of having too much body fat, which can increase the risk of various health problems.
Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.
The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.
Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.
Appetite regulation refers to the physiological and psychological processes that control and influence the desire to eat food. This complex system involves a variety of hormones, neurotransmitters, and neural pathways that work together to help maintain energy balance and regulate body weight. The hypothalamus in the brain plays a key role in appetite regulation by integrating signals from the digestive system, fat cells, and other organs to adjust feelings of hunger and fullness.
The hormones leptin and ghrelin are also important regulators of appetite. Leptin is released from fat cells and acts on the hypothalamus to suppress appetite and promote weight loss, while ghrelin is produced in the stomach and stimulates appetite and promotes weight gain. Other factors that can influence appetite regulation include stress, emotions, sleep patterns, and cultural influences.
Abnormalities in appetite regulation can contribute to the development of eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating disorder, as well as obesity and other health problems. Understanding the mechanisms of appetite regulation is an important area of research for developing effective treatments for these conditions.
Hyperphagia is a medical term that describes excessive eating or increased appetite, often to the point of compulsive overeating. It's more than just a simple increase in hunger or appetite; it's characterized by consuming large amounts of food beyond what is needed for normal growth and health.
This condition can be associated with several medical conditions. For instance, it's a common symptom in Prader-Willi syndrome, a genetic disorder that affects appetite, growth, and cognitive development. It can also occur in certain types of brain injuries or disorders affecting the hypothalamus, a part of the brain that regulates hunger and fullness signals.
However, it's important to note that hyperphagia should not be confused with binge eating disorder, another eating disorder characterized by consuming large amounts of food in a short period of time, but without the feeling of loss of control that is typical of binge eating.
As always, if you or someone else is experiencing symptoms of hyperphagia, it's important to seek medical advice to identify and treat any underlying conditions.
C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.
The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.
C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.
One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.
Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.
I'm sorry for any confusion, but "Rats, Zucker" is not a standard medical term or abbreviation in human medicine. It seems to be an incorrect combination of two terms from the field of laboratory animal science.
1. "Rats" are commonly used laboratory animals.
2. "Zucker" is a surname and also refers to a strain of laboratory rats, specifically the Zucker Diabetic Fatty (ZDF) rat, which is a model for studying type 2 diabetes mellitus.
If you have any questions related to human medicine or healthcare, I would be happy to help clarify those for you.
Peptide hormones are a type of hormone consisting of short chains of amino acids known as peptides. They are produced and released by various endocrine glands and play crucial roles in regulating many physiological processes in the body, including growth and development, metabolism, stress response, and reproductive functions.
Peptide hormones exert their effects by binding to specific receptors on the surface of target cells, which triggers a series of intracellular signaling events that ultimately lead to changes in cell behavior or function. Some examples of peptide hormones include insulin, glucagon, growth hormone, prolactin, oxytocin, and vasopressin.
Peptide hormones are synthesized as larger precursor proteins called prohormones, which are cleaved by enzymes to release the active peptide hormone. They are water-soluble and cannot pass through the cell membrane, so they exert their effects through autocrine, paracrine, or endocrine mechanisms. Autocrine signaling occurs when a cell releases a hormone that binds to receptors on the same cell, while paracrine signaling involves the release of a hormone that acts on nearby cells. Endocrine signaling, on the other hand, involves the release of a hormone into the bloodstream, which then travels to distant target cells to exert its effects.
Resistin is a hormone-like substance that is primarily produced by adipose (fat) cells in mammals and has been implicated in the development of insulin resistance, which is a condition that can lead to type 2 diabetes. It is also known as "adipose tissue-specific secretory factor" or ADSF.
Resistin is thought to play a role in regulating glucose metabolism and insulin sensitivity by affecting the function of insulin-responsive cells, such as muscle and liver cells. In particular, resistin has been shown to interfere with the ability of insulin to stimulate glucose uptake in these cells, leading to reduced insulin sensitivity and increased blood glucose levels.
Resistin is found at higher levels in people who are overweight or obese, and its levels have been linked to the development of insulin resistance and type 2 diabetes. However, the exact role that resistin plays in these conditions is not fully understood, and more research is needed to determine its precise mechanisms of action and potential therapeutic uses.
Leptin receptor
Louis Tartaglia
Teleost leptins
Michael Warren Schwartz
Neuropeptide Y
Adiponectin
Douglas L. Coleman
Type I cytokine receptor
Puberty
Liver X receptor alpha
Leptin
Mike Phillips (speech recognition)
Low-density lipoprotein receptor-related protein 8
Growth hormone secretagogue receptor
SOCS3
Ana Domingos
DGKZ
Hyperemesis gravidarum
Periventricular nucleus
Hypocretin (orexin) receptor 2
Estrogen receptor alpha
Glucagon-like peptide-1 receptor
JD5037
Melatonin
Eating
Anorexia nervosa
Acquired generalized lipodystrophy
Free fatty acid receptor 3
Agouti-related peptide
LYN
Leptin receptor - Wikipedia
Leptin receptor deficiency: MedlinePlus Genetics
Orphanet: Obesity due to leptin receptor gene deficiency
Alexa Fluor® 647 Mouse Anti-Human Leptin Receptor (CD295)
Frontiers | Leptin Receptor q223r Polymorphism Influences Clostridioides difficile Infection-Induced Neutrophil CXCR2...
Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin...
Leptin Receptor | BioVendor R&D
Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia | Egyptian Journal of Medical...
Leptin receptor activity in the nucleus of the solitary tract increases forebrain leptin sensitivity - Advanced Targeting...
Reactome | Phosphorylated STAT3 Dissociates from Leptin Receptor
JCI Insight - Citations to PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and...
Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: a report from...
Rat LEPR(Leptin Receptor) ELISA Kit - AGTC Sequencing
Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in...
A simplified diagram of the regulation of feeding behavior at the level... | Download Scientific Diagram
Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons
Association study of leptin and leptin receptor gene polymorphisms with diabetes type 2 and obesity
Role of estrogen receptor-α and -β in regulating leptin expression in 3T3-L1 adipocytes - Korea University
Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice - Inscopix
Hunger enhances food-odour attraction through a neuropeptide Y spotlight | Nature
BioWorld Science: The Daily Drug R&D News Source
Recent advances in the genetics of severe childhood obesity | Archives of Disease in Childhood
Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase. -...
Leptin receptor defect with diabetes causes skeletal muscle atrophy in female obese Zucker rats where peculiar depots networked...
Loop | Publication Impact | Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic...
Novel variant in the leptin receptor (LEPR) gene and its association with fat quality, odour and flavour in sheep | Gunawan |...
Prescription weight-loss drugs: Can they help you? - Mayo Clinic
Serum leptin and serum leptin/serum leptin receptor ratio imbalance in obese rheumatoid arthritis patients positive for anti...
The effect of four weeks restricted diet on serum soluble leptin receptor levels and adipocyte leptin receptor density in...
GHR is a member of the cytokine receptor superfamily that includes prolactin receptor, erythropoietin receptor, leptin receptor...
LEPR17
- Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor, a protein that in humans is encoded by the LEPR gene. (wikipedia.org)
- Leptin receptor deficiency is caused by mutations in the LEPR gene. (medlineplus.gov)
- LEPR gene mutations that cause leptin receptor deficiency prevent the receptor from responding to leptin, leading to the excessive hunger and weight gain associated with this disorder. (medlineplus.gov)
- Because hypogonadotropic hypogonadism occurs in leptin receptor deficiency, researchers suggest that leptin receptor signaling is also involved in regulating the body's response to hormones that control sexual development, and that this response is affected by LEPR gene mutations. (medlineplus.gov)
- We have previously reported that a single nucleotide polymorphism (SNP) in leptin receptor (LEPR), present in up to 50% of people, influenced CDI-induced neutrophil CXCR2 expression and tissue neutrophilia. (frontiersin.org)
- However, we detected histone H3 methylation and acetylation in the leptin receptor gene, Lepr, following treatment with both drugs. (nih.gov)
- The mutation in leptin receptor (LEPR) gene causes splicing abnormality that resulted in truncated receptor, aberrant signal transduction, leptin resistance, and obesity. (ajol.info)
- This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on phenotype and leptin level between obese and control groups in Yogyakarta population. (ajol.info)
- Because radiation at a young age may affect the hypothalamus causing leptin receptor insensitivity, we hypothesized that a polymorphism in the leptin receptor (LEPR) gene, Gln223Arg, might influence susceptibility to obesity in survivors of childhood ALL. (duke.edu)
- Description: A sandwich quantitative ELISA assay kit for detection of Rat Leptin Receptor (LEPR) in samples from serum, plasma, tissue homogenates or other biological fluids. (agctsequencing.com)
- Description: A competitive ELISA for quantitative measurement of Rat Leptin receptor(LEPR) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. (agctsequencing.com)
- Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Leptin Receptor (LEPR) in serum, plasma, tissue homogenates and other biological fluids. (agctsequencing.com)
- It is therefore possible that variation in the leptin receptor gene (LEPR) may contribute to obesity and influence birth weight. (ox.ac.uk)
- This study was performed to investigate the prevalence and association A19G and K109R polymorphisms in leptin (LEP) and leptin receptor genes (LEPR) with diabetes and obesity in Yazd, Iran. (healthbiotechpharm.org)
- Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. (inscopix.com)
- Novel variant in the leptin receptor (LEPR) gene and its association with fat quality, odour and flavour in sheep," Journal of the Indonesian Tropical Animal Agriculture , vol. 44, no. 1, pp. 1-9, Mar. 2019. (undip.ac.id)
- Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. (biomedcentral.com)
Hypothalamus7
- The leptin hormone regulates adipose-tissue mass through hypothalamus effects on hunger and energy use. (wikipedia.org)
- In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect hunger and help produce a feeling of fullness (satiety). (medlineplus.gov)
- Long forms of OB-R transcripts were reported to be expressed predominantly in regions of the hypothalamus which provides evidence that Leptin receptor is important in body weight regulation. (biovendor.com)
- Leptin receptor is important in leptin signal transduction that is located mainly in the hypothalamus. (ajol.info)
- The full-length leptin receptor, that is believed to transmit the leptin signal, is expressed in human hypothalamus. (johnshopkins.edu)
- According to that theory, the hypothalamus controls food intake via receptors that measure glucose concentrations in the blood in order to keep blood glucose concentrations constant. (frontiersin.org)
- Therefore, the anorexigenic effect exerted by the CBD could be the result of a multitarget mechanism, involving the whole endocannabinoid receptor system, particularly in the hypothalamus. (researchgate.net)
Obesity20
- Variations in the leptin receptor have been associated with obesity and with increased susceptibility to Entamoeba histolytica infections. (wikipedia.org)
- The db/db mouse is a model of obesity, diabetes, and dyslipidemia wherein leptin receptor activity is deficient because the mice are homozygous for a point mutation in the gene for the leptin receptor. (wikipedia.org)
- Leptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. (medlineplus.gov)
- Leptin receptor deficiency is a rare cause of obesity. (medlineplus.gov)
- Andiran N, Celik N, Andiran F. Homozygosity for two missense mutations in the leptin receptor gene (P316:W646C) in a Turkmenian girl with severe early-onset obesity. (medlineplus.gov)
- Dubern B, Clement K. Leptin and leptin receptor-related monogenic obesity. (medlineplus.gov)
- Polymorphism of rs1137100 (K109R) and rs1137101 (Q223R) were associated with obesity and leptin level. (ajol.info)
- Scholars@Duke publication: Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. (duke.edu)
- Leptin acts in the brain to prevent obesity. (nih.gov)
- As POMC neurons prevent obesity, their disinhibition by leptin action on presynaptic GABAergic neurons probably mediates, at least in part, leptin's antiobesity effects. (nih.gov)
- 2017). 'Association study of leptin and leptin receptor gene polymorphisms with diabetes type 2 and obesity', Health Biotechnology and Biopharma (HBB) , 1(2), pp. 61-69. (healthbiotechpharm.org)
- Rhythm Pharmaceuticals Inc. has presented preclinical data on its new drug candidate, RM-718, a next-generation melanocortin MC4 receptor (MC4R) agonist for weekly administration with a potential development path for hypothalamic obesity. (bioworld.com)
- One of the five possible mechanisms of leptin resistance in human obesity is the defect in the leptin receptor (Ob-R). Evidence has accumulated that leptin-binding activity in human serum is related to a soluble form of the leptin receptor, and restriction of energy intake resulted a decrease in circulating leptin levels. (ui.ac.id)
- Another possible anti-obesity target is the CB2 receptor. (researchgate.net)
- Some studies have linked intake of a GF diet to reduced obesity and T2D and suggested a role in reducing leptin- and insulin-resistance and increasing beta-cell volume. (mdpi.com)
- People with rare mutations of genes in the leptin-signaling pathway (e.g., complete deficiencies of leptin or its receptor) have a very high likelihood of developing obesity. (cdc.gov)
- Antagonizing the Leptin Receptor in Obesity. (cdc.gov)
- Leptin was once hailed as a treatment for most cases of childhood obesity but quickly lost favor when resistance to leptin was noted. (cdc.gov)
- Most genes causing monogenic obesity are implicated in the central energy regulatory circuits of the leptin-melanocortin pathway. (cdc.gov)
- [ 10 ] Mutations of genes encoding either leptin or the leptin receptor underlie isolated cases of autosomally transmitted idiopathic hypogonadotropic hypogonadism associated with early-onset obesity. (medscape.com)
Soluble form of the Leptin receptor1
- The soluble form of the Leptin receptor, OB R contains no intracellular motifs or transmembrane residues, thus it consists entirely of the extracellular ligand binding domain of the receptor. (biovendor.com)
Neurons6
- In hypothalamic neurons, adequate leptin receptor function and subsequent regulation of energy metabolism and body weight depends on interactions of the receptor with gangliosides in the cell membrane. (wikipedia.org)
- Leptin-Saporin (Lep-Sap) injections were used to delete ObR- expressing neurons in the NTS of 300g male Sprague Dawley rats. (atsbio.com)
- The underlying neurocircuitry responsible for this is poorly understood, in part because of incomplete knowledge regarding first-order, leptin-responsive neurons. (nih.gov)
- To address this, we and others have been removing leptin receptors from candidate first-order neurons. (nih.gov)
- Leptin, working directly on presynaptic GABAergic neurons, many of which appear not to express AgRP, reduces inhibitory tone to postsynaptic POMC neurons. (nih.gov)
- Mice that lack neuropeptide Y (NPY) or NPY receptor type 5 (NPY5R) fail to prefer food odours over pheromones after fasting, and hunger-dependent food-odour attraction is restored by cell-specific NPY rescue in AGRP neurons. (nature.com)
Isoforms of the Leptin receptor1
- Alternate splicing from a single gene derives the six isoforms of the Leptin receptor. (biovendor.com)
Protein9
- Like other cytokine receptors, Leptin receptor protein has three different regions: i) extracellular, ii) trans-membrane, and iii) intracellular. (wikipedia.org)
- This gene provides instructions for making a protein called the leptin receptor, which is involved in the regulation of body weight. (medlineplus.gov)
- Leptin receptor (OB R) was identified as a leptin binding protein (Leptin, the product of the ob gene, is a single chain 16 kDa protein consisting of 146 amino acid residues. (biovendor.com)
- Leptin, the protein product of the ob gene, is a hormone that is secreted principally by adipose tissue (adipocyte-derived hormone). (researchgate.net)
- Conclusions In conclusion, the findings of this study indicate that plasma ghrelin level increases and leptin level decreases and growth accelerates because of an increase in appetite and daily calories, carbohydrate and protein amount in children with nutritional iron deficiency anemia after iron therapy. (researchgate.net)
- Anti-CCP anti cyclic citrullinated peptide antibodies, BMI body mass index, ESR erythrocyte sedimentation rate, CRP C-reactive protein, DAS-28 disease activity index in 28 joints, sLepR soluble leptin receptor, FM fat mass, HOMA-IR , homeostatic model assessment-insulin resistance. (biomedcentral.com)
- This second base substitution changed a glutamine to an arginine at position 223 of the leptin receptor protein. (johnshopkins.edu)
- Results Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV 1 and paraoxonase 3 was positively associated therewith. (lu.se)
- Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. (lu.se)
Suggest that leptin1
- These data suggest that leptin- induced inhibition of food intake is mediated by an integrated network involving both the forebrain and hindbrain and that activation of NTS ObRb lowers the threshold for leptin responsiveness in the forebrain. (atsbio.com)
Circulating leptin levels3
- Observational studies comparing circulating leptin levels between COPD patients and healthy controls were included. (karger.com)
- Circulating leptin levels were correlated with the body mass index (BMI) as well as percent fat mass in stable COPD patients. (karger.com)
- Most studies indicated that circulating leptin levels in stable COPD patients were not significantly different from those in healthy controls when adjusted for gender and BMI, whilst leptin levels tended to elevate in exacerbation groups. (karger.com)
Polymorphism2
- Maternal genotype for the Gln223Arg leptin receptor gene polymorphism showed no significant association with foetal birth weight (adjusted for gestational length) or with maternal BMI during first trimester (adjusted for age) in either population group. (ox.ac.uk)
- A sequence polymorphism (A→G) was detected at position 668 of the leptin receptor cDNA. (johnshopkins.edu)
Deficiency5
- People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. (medlineplus.gov)
- The aim of this study was to investigate the effect of iron therapy on appetite, growth and plasma ghrelin and leptin levels in children aged between 12 and 24 months with isolated nutritional iron deficiency anemia. (researchgate.net)
- The increase in appetite and acceleration on growth in iron deficiency anemia might result from decreased leptin and increased plasma ghrelin levels. (researchgate.net)
- Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase. (nin.nl)
- For people with leptin deficiency, treatment with leptin leads to sustained improvement in adiposity. (cdc.gov)
Adipocyte2
- BACKGROUND: Leptin is an adipocyte secreted hormone involved in regulation of body weight and metabolism in man. (ox.ac.uk)
- Diet of 40 % normal daily calorie for 4 weeks decreased soluble leptin receptor level, but increased adipocyte leptin receptor density of the adipose tissue of rat adventitial aorta. (ui.ac.id)
Cytokine5
- The extracellular part has 5 functional domains: i) membrane distal 1st cytokine receptor homology (CRH1), ii) Immunoglobulin like (Ig), iii) 2nd cytokine receptor homology (CRH2) and iv) two membrane proximal fibronectine type-III (FNIII) domains. (wikipedia.org)
- It acts through the leptin receptor (LEP-R), a single-transmembrane-domain receptor of the cytokine receptor family. (wikipedia.org)
- OB R was found to be a member of the class I cytokine receptor family with a large extracellular domain comprising 816 amino acid residues. (biovendor.com)
- GH is usually a four helix bundle cytokine with structural similarity to prolactin, erythropoietin, T16Ainh-A01 leptin, and several IL and other cytokines (4). (imacst.com)
- The cytokine receptors lack intrinsic kinase activity and require interaction with members of the Jak family of intracellular signaling molecules. (jneurosci.org)
Hormone8
- LEP-R functions as a receptor for the fat cell-specific hormone leptin. (wikipedia.org)
- The leptin hormone and its receptor, also known as maternal plasma leptin, play developmental roles during pregnancy. (wikipedia.org)
- The leptin receptor is turned on (activated) by a hormone called leptin that attaches (binds) to the receptor, fitting into it like a key into a lock. (medlineplus.gov)
- Leptin is a hormone that regulates homeostasis energy through the central- peripheral mechanism as well as regulates hunger and satiety. (ajol.info)
- thus, leptin is often referred to as the 'satiety hormone. (researchgate.net)
- The adiposity hormone, leptin, plays an important role in the control of glucose metabolism by its action in the brain. (healthbiotechpharm.org)
- These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. (wjgnet.com)
- In one patient, isolated bioinactive luteinizing hormone (LH) was present as a result of a homozygous mutation in the LH beta subunit gene, which prevented binding of LH to its receptor. (medscape.com)
Glucose2
- 12 Other important effects of leptin include increase in glucose utilization, inhibition of lipogenesis, stimulation of fatty acid oxidation, and reduction of trigliceride accumulation in liver and skeletal muscles, accounting for leptin's insulin-sensitizing properties. (researchgate.net)
- Plasma levels of glucose, leptin and insulin are elevated in males. (jax.org)
Effects of leptin2
- The mechanisms behind weight increase with ruxolitinib is incompletely understood, although decreased adipose tissue lipolysis and increased appetite due to blocking the effects of leptin in the hypothalam. (researchgate.net)
- The effects of leptin are reducing body adiposity, food intake and improving insulin sensitivity in peripheral tissue by indirect mechanism. (healthbiotechpharm.org)
Adiponectin3
- We investigated the effects of the estrogen receptor-α (ERα) and -β (ERβ) in the regulation of leptin, resistin, and adiponectin expression in 3T3-L1 adipocytes. (korea.ac.kr)
- Serum adipokines including high molecular weight (HMW)-adiponectin, leptin, and soluble leptin receptor (sOB-R) were measured at the follow-up visit (2002-2003). (cdc.gov)
- Conclusions: Our findings suggest that molybdenum was associated with favorable profiles of HMW-adiponectin, leptin, and sOB-R. Exposures to cadmium, cesium, and lead were associated with adverse adipokine profiles. (cdc.gov)
Adiposity1
- Soluble Leptin receptor levels are indirectly proportional to adiposity and are increased in females versus males. (biovendor.com)
ELISA1
- Soluble leptin receptor level was measured by ELISA and leptin receptor density by using immuno-histochemistry. (ui.ac.id)
Mutation1
- The mutation responsible for the defect in the leptin receptor in db/db mice was not detected in any obese human, nor was the fa/fa rat mutation. (johnshopkins.edu)
Adipose-tissue2
- 13 Leptin is synthesized and released predominantly by adipocytes, and its serum concentrations correlate positively with body mass index (BMI) and the amount of adipose tissue. (researchgate.net)
- Aim of this study is to examine the difference of serum soluble leptin receptor level and leptin receptor density in rat adipose tissue of adventitial aorta after four weeks treated with different restricted diets. (ui.ac.id)
Ligand5
- in 1994, (which involved a reverse genetic/positional cloning strategy to clone ob and db), Rudolph Leibel, working with collaborators also at Millennium Pharmaceuticals and colleague Streamson Chua, confirmed cloning of the leptin receptor by demonstrating that an apparent leptin receptor cloned from a choroid plexus library using leptin as ligand, mapped to a physical map that included db and fa. (wikipedia.org)
- Ig domain interacts with Leptin and is essential for conformational change in the receptor upon ligand binding. (wikipedia.org)
- The structure of the quaternary complex of the complete extracellular part in complex with the cognate ligand Leptin (i.e. 2 receptor and 2 ligand) has been solved by both electron microscopy and SAXS. (wikipedia.org)
- Another method of inhibit surface area receptor signaling has been antireceptor antibodies that stop either ligand binding or receptor activation (30, 31). (imacst.com)
- The condyles were analyzed histologically, histomorphometrically, and immunohistochemically using the antibodies for bone sialoprotein (BSP), osteocalcin (OCC) and receptor activator of nuclear factor kappa-B ligand (RANKL). (bvsalud.org)
Hypogonadotropic hypogonadism1
- [ 11 ] Several loss-of-function mutations of the GnRH receptor gene leading to GnRH resistance and autosomally transmitted hypogonadotropic hypogonadism have been described. (medscape.com)
Resistance2
- These results provide evidence that the leptin resistance observed in obese humans is not due to a defect in the leptin receptor. (johnshopkins.edu)
- Leptin levels will fall increasing hunger while cortisol is increasing insulin resistance. (robbwolf.com)
Melanocortin1
- Radionetics Oncology Inc. has patented new melanocortin MC2 receptor ligands reported to be useful for the diagnosis and treatment of cancer. (bioworld.com)
Inhibition1
- There was a dose-dependent inhibition of food intake in Blk-Sap rats, but only 0.5 μg leptin inhibited intake of Lep-Sap rats. (atsbio.com)
MRNA1
- There was no difference in the amount of leptin-receptor mRNA in seven lean (BMI 23.3 ± 0.9 kg/m 2 ) and eight obese (BMI 36.9 ± 1.5) subjects as determined by reverse transcription-polymerase chain reaction. (johnshopkins.edu)
Placenta2
- Leptin receptors have been identified in the placenta of pregnant women and also in fetal tissues. (wikipedia.org)
- Placenta leptin levels correlate positively with birth weight. (ox.ac.uk)
Obese2
- Body mass index, waist circumference and leptin level in obese group were significantly higher than those in the control group. (ajol.info)
- Leptin-receptor gene expression in hypothalamic tissue from lean and obese humans was examined. (johnshopkins.edu)
Rats2
- Loss of NTS ObR was confirmed with RNAScope in situ hybridization and pSTAT3 response to peripheral leptin in representative Lep- Sap rats. (atsbio.com)
- To test leptin responsiveness rats were food deprived for 5 hours and at 5 p.m. they received 3V injections of 0, 0.05, 0.1, 0.25 or 0.5 μg leptin. (atsbio.com)
ObRb2
- Summary: We previously reported that fourth ventricle infusions of leptin that cause weight loss are associated with an increase in hypothalamic phosphorylation of signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor (ObRb) activation, implying an integrated response to central leptin. (atsbio.com)
- This study tested the impact of ObRb activity in the nucleus of the solitary tract (NTS) on sensitivity to leptin in the forebrain. (atsbio.com)
Phenotype2
- We show that disruption of p110α and p110β subunits in leptin receptor cells (LRΔα+β) produces a lean phenotype associated with increased energy expenditure, locomotor activity, and thermogenesis. (jci.org)
- Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis. (medscape.com)
Increases1
- Insulin signaling through the insulin receptor increases linear growth through effects on bone and the GH-IGF-1 axis. (medscape.com)
Metabolic2
- The role of PI3K in leptin physiology has been difficult to determine due to its actions downstream of several metabolic cues, including insulin. (jci.org)
- Blunted PI3K in leptin receptor (LR) cells enhanced leptin sensitivity in metabolic regulation due to increased basal hypothalamic pAKT, leptin-induced pSTAT3, and decreased PTEN levels. (jci.org)
Food intake1
- Leptin is an important regulator of food intake and energy expenditure. (karger.com)
Signaling6
- These data support several shared transcriptional targets of Li and VPA, and provide evidence suggesting leptin signaling as an epigenetic target of two mood stabilizers. (nih.gov)
- Additional work could help clarify whether leptin signaling in the brain has a role in the therapeutic action of Li and VPA in bipolar disorder. (nih.gov)
- Here, we used a series of mouse models to dissociate the roles of specific PI3K catalytic subunits and of insulin receptor (InsR) downstream of leptin signaling. (jci.org)
- demonstrate that anti-GHRmAb 18.24 also inhibits rabbit and human GHR signaling and inducible receptor proteolysis. (imacst.com)
- GH-dependent signaling is usually activated by GHR's adoption of the dimerized construction that activates the receptor-associated cytoplasmic tyrosine kinase, Janus kinase 2 (JAK2), and additional kinases and following engagement from the sign transducer and activator of transcription (STAT), sTAT5A/B particularly, ERK, phosphatidylinositol-3 kinase, and additional pathways (18C25). (imacst.com)
- [ 4 ] Of note, anosmin may enhance fibroblast growth factor signaling through the fibroblast growth factor receptor 1. (medscape.com)
CD2953
- Multicolor flow cytometric analysis of Leptin Receptor (CD295) on human mononuclear cells. (bdbiosciences.com)
- The leucocytes were washed and stained with FITC Mouse Anti-Human CD14 (Cat No. 555397/557153/561712), BD Horizon™ V450 Mouse Anti-Human CD19 (Cat No. 644491) antibodies and either Alexa Fluor® 647 Mouse IgG2b, κ Isotype Control (Cat No. 557903) or Alexa Fluor® 647 Mouse Anti-Human Leptin Receptor (CD295) antibody (Cat No. 564376). (bdbiosciences.com)
- The flow cytometric dot plots show the correlated expression patterns of CD19 (Upper Panels) or CD14 (Lower Panels) versus Leptin Receptor (CD295) [or Ig Isotype control staining] for gated events with the forward and side light-scatter characteristics of viable mononuclear leucocytes. (bdbiosciences.com)
Gln223Arg2
- OBJECTIVE: This study investigates the influence of the leptin receptor gene variant Gln223Arg (A→G, 668), on maternal body mass index (BMI), foetal gestational length and birth weight in a cohort of 455 healthy pregnant women of Asian Indian (India, Bangladesh, Pakistan) and UK/Irish origin. (ox.ac.uk)
- CONCLUSION: These results suggest that the Gln223Arg variant in the maternal leptin receptor gene does not explain the association between placental leptin levels and birth weight, and is not associated with variation in maternal BMI in early pregnancy in our sample. (ox.ac.uk)
Mechanism1
- The normal regulatory mechanism of leptin is maintained in stable COPD patients despite weight loss. (karger.com)
Levels4
- they increase leptin levels during pregnancy thereby aiding the fetal development. (wikipedia.org)
- Leptin receptor levels are highest in infants, decrease into adolescence, and remain relatively stable throughout adulthood. (biovendor.com)
- A positive correlation between leptin and tumor necrosis factor (TNF)-α levels was found in COPD exacerbations, while it disappeared in patients with stable disease. (karger.com)
- Leptin and BDNF were significantly higher, and neurotensin levels were significantly lower in D-IBS(+) than in controls. (hindawi.com)
Regulatory1
- CRH1 domains is not essential for Leptin binding, but may have regulatory roles. (wikipedia.org)
Prokineticin2
- [ 7 ] Homozygous, heterozygous or compound heterozygous mutations of the prokineticin receptor 2 have also been associated with Kallmann syndrome. (medscape.com)
- [ 8 ] Digenic inheritance has been suggested in an individual carrying heterozygous mutations of prokineticin receptor 2 and KAL1 . (medscape.com)
Significantly1
- The soluble leptin receptor in group treated with 40% of normal daily calori diet was found significantly lower than control (p = 0.02). (ui.ac.id)
Regulator1
- Leptin receptor may act as a negative regulator of Leptin activity and it may maintain a pool of available bioactive Leptin by binding and delaying its clearance from circulation. (biovendor.com)
Peripheral1
- At the recent American College of Neuropsychopharmacology meeting, Trevena Inc. presented preclinical data for the novel selective sphingosine 1-phosphate S1P1 receptor modulator TRV-045, being developed for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). (bioworld.com)
Tissues1
- On the other hand, leptin receptor density in adipose tissues was higher in restricted diet group than control. (ui.ac.id)
Populations1
- There are two main neuronal populations in the hypothalamic arcuate nucleus that are sensitive to signals indicating systemic fuel availability (e. g., leptin, ghrelin and insulin). (researchgate.net)