Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.Receptors, Leptin: Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Hypothalamus: Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.Eating: The consumption of edible substances.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Mice, Obese: Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Adiponectin: A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.Ghrelin: A 28-amino acid, acylated, orexigenic peptide that is a ligand for GROWTH HORMONE SECRETAGOGUE RECEPTORS. Ghrelin is widely expressed but primarily in the stomach in the adults. Ghrelin acts centrally to stimulate growth hormone secretion and food intake, and peripherally to regulate energy homeostasis. Its large precursor protein, known as appetite-regulating hormone or motilin-related peptide, contains ghrelin and obestatin.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Pro-Opiomelanocortin: A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).Fasting: Abstaining from all food.Neuropeptide Y: A 36-amino acid peptide present in many organs and in many sympathetic noradrenergic neurons. It has vasoconstrictor and natriuretic activity and regulates local blood flow, glandular secretion, and smooth muscle activity. The peptide also stimulates feeding and drinking behavior and influences secretion of pituitary hormones.Body Mass Index: An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)Adipokines: Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.Injections, Intraventricular: Injections into the cerebral ventricles.Blood Glucose: Glucose in blood.Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Agouti-Related Protein: A secreted protein of approximately 131 amino acids that is related to AGOUTI SIGNALING PROTEIN and is also an antagonist of MELANOCORTIN RECEPTOR activity. It is expressed primarily in the HYPOTHALAMUS and the ADRENAL GLAND. As a paracrine signaling molecule, AGRP is known to regulate food intake and body weight. Elevated AGRP has been associated with OBESITY.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Anorexia: The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA.Adiposity: The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Appetite Regulation: Physiologic mechanisms which regulate or control the appetite and food intake.Hyperphagia: Ingestion of a greater than optimal quantity of food.Mice, Inbred C57BLRats, Zucker: Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene.Peptide Hormones: Hormones synthesized from amino acids. They are distinguished from INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS in that their actions are systemic.Resistin: A 12-kDa cysteine-rich polypeptide hormone secreted by FAT CELLS in the ADIPOSE TISSUE. It is the founding member of the resistin-like molecule (RELM) hormone family. Resistin suppresses the ability of INSULIN to stimulate cellular GLUCOSE uptake.Hunger: The desire for FOOD generated by a sensation arising from the lack of food in the STOMACH.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)TexasPsoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.Access to Information: Individual's rights to obtain and use information collected or generated by others.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)Editorial Policies: The guidelines and policy statements set forth by the editor(s) or editorial board of a publication.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.JapanMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Abstracting and Indexing as Topic: Activities performed to identify concepts and aspects of published information and research reports.
  • Leptin regulates the pro-inflammatory response in human epidermal keratinocytes. (nih.gov)
  • Describes a cellular signaling pathway in which CASK, a structural girder of cell junctions, directly enters the nucleus and thereby regulates gene expression. (ebscohost.com)
  • However, other transcription factors such as members of the SMAD and NFAT families may be involved and need further investigation to better define how leptin regulates their activities and their relevance for Leydig cells function. (deepdyve.com)
  • The present study aims to examine how acute central infusion of leptin regulates peripheral lipid metabolism, as assessed by markers indicative of their mobilization and utilization. (biomedsearch.com)
  • It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes, thus protecting them from lipotoxicity. (pnas.org)
  • If prevention of obesity is not the primary function of leptin, what is its physiologic mission? (pnas.org)
  • Here, we propose that an important physiologic function of leptin is to regulate in nonadipocytes the intracellular homeostasis of fatty acids (FA) and triglycerides (TG) so as to maintain a sufficient supply of FA for essential cell functions while avoiding TG overload. (pnas.org)
  • Taken together these findings give a better understanding of the function of leptin and the regulatory mechanisms of leptin expression in human placental trophoblast and further support the importance of leptin in the biology of reproduction. (conicet.gov.ar)
  • Little is known about variation in leptin levels during pregnancy or the level or function of leptin in the growing fetus and infants. (aappublications.org)
  • Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients. (diabetesjournals.org)
  • The purpose of this study was to evaluate a polymorphism in the 3' untranslated region of the TNFR2 gene on chromosome 1 in relation to BMI, leptin levels, and insulin resistance. (diabetesjournals.org)
  • In the study sample, carriers of the A2 allele (n = 18) showed significantly increased BMI, fat mass, waist-to-hip ratio, serum total and VLDL triglyceride levels, and leptin levels and had a lower insulin sensitivity index than noncarriers of the A2 variant (n = 15). (diabetesjournals.org)
  • CONCLUSIONS: The presence of the A2 allele in the TNFR2 gene may predispose subjects to obesity and higher leptin levels, which may in turn predispose them to insulin resistance or vice versa. (diabetesjournals.org)
  • Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic β-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. (diabetesjournals.org)
  • Dysregulation of this adipoinsular axis with the establishment of leptin resistance in pancreatic β-cells may lead to hyperinsulinemia, which could contribute to obesity and insulin resistance. (diabetesjournals.org)
  • However, we previously determined that leptin increases binding of STAT5b to the upstream sequences of the rat preproinsulin 1 promoter ( 6 ) and inhibits insulin biosynthesis via transcriptional repression ( 5 ). (diabetesjournals.org)
  • In addition, there was no association between plasma leptin and the insulin: glucose ratio (an index of insulin sensitivity). (unboundmedicine.com)
  • This is of relevance when considering leptin therapy and may partly explain the relationship among leptin, proinflammatory cytokines, insulin resistance, and obesity. (jimmunol.org)
  • OBJECTIVE -To investigate whether leptin-induced improvements in glycemic control, hyperlipidemia, and insulin sensitivity in hypoleptinemic patients with generalized lipodystrophies are accompanied by reduction in intrahepatic and intramyocellular lipid (IMCL) accumulation. (diabetesjournals.org)
  • RESEARCH DESIGN AND METHODS -We examined the effects 8-10 months of subcutaneous leptin replacement therapy on insulin sensitivity, IMCL, and intrahepatic lipid content in two patients with acquired generalized lipodystrophy and one patient with congenital generalized lipodystrophy. (diabetesjournals.org)
  • Insulin stimulated glucose uptake during 60-120 min of the euglycemic clamp studies, and the rate of glucose disappearance during the insulin tolerance test nearly doubled with leptin therapy. (diabetesjournals.org)
  • CONCLUSIONS -Reduction in IMCL and intrahepatic lipid content may partly explain leptin-induced improvement in insulin sensitivity in patients with generalized lipodystrophy. (diabetesjournals.org)
  • These signals are transmitted by hormones-such as leptin, insulin, and ghrelin-and other small molecules. (cdc.gov)
  • In obesity, similar to resistance of insulin in type 2 diabetes, a decreased sensitivity to leptin occurs, resulting in an inability to detect satiety despite high energy stores. (wikipedia.org)
  • Leptin promotes pulmonary fibrosis development by inhibiting autophagy via PI3K/Akt/mTOR pathway. (nih.gov)
  • Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways (By similarity). (uniprot.org)
  • The hexosamine biosynthetic pathway is a cellular 'sensor' of energy availability and mediates the effects of glucose on the expression of several gene products. (nih.gov)
  • In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic β-cells. (diabetesjournals.org)
  • Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate Cells via JAK2-STAT3 Pathway to Protect against Hepatic Fibrosis. (ebscohost.com)
  • Here, we report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. (biomedcentral.com)
  • To illustrate the concept of oscillation within a biological pathway we have chosen the leptin pathway as an example. (biomedcentral.com)
  • This leptin signal transduction pathway is well studied and can be found in a number of private and public databases. (biomedcentral.com)
  • We have extracted the description along with the cartoon illustrating the leptin pathway from the Kyoto Encyclopedia of Genes and Genomes (KEGG)[ 8 ], We have scaled, smoothed, and assigned to most likely phase class the data sets with microarray expression profiles from the previously published studies (see Methods). (biomedcentral.com)
  • This leptin-induced STAT3 translocation pattern proved to be distinct from that induced by interleukin-6, another cytokine using STAT3 in its signaling pathway. (jneurosci.org)
  • Leptin also exerts an antiapoptotic action in placenta and this effect is mediated by the MAPK pathway. (conicet.gov.ar)
  • We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus. (abertay.ac.uk)
  • Leptin-induced protection against myocardial ischemia-reperfusion (I/R) injury involves the activation of the reperfusion injury salvage kinase pathway, incorporating phosphatidylinositol 3-kinase-Akt/protein kinase B and p44/42 MAPK, and the inhibition of the mitochondrial permeability transition pore (MPTP). (physiology.org)
  • As described for other cardioprotective treatments ( 14 ), leptin-induced protection was found to involve the activation of the reperfusion injury salvage kinase (RISK) pathway, through phosphatidylinositol 3-kinase (PI3K)-cellular Akt/protein kinase B (Akt) and p44/42 mitogen-activated protein kinase, and the suppression of mitochondrial permeability transition pore (MPTP) opening ( 24 ), mechanisms regarded as prerequisites for cardioprotection ( 14 ). (physiology.org)
  • The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a vital role in modulating the expression of stress-responsive genes by transducing signals received at the cell surface to the nucleus ( 7 , 17 ). (physiology.org)
  • Given that it has been proposed that the JAK/STAT pathway may play a vital role in cardioprotection (3-5, 26 ), we investigated whether the cardioprotective actions of leptin, when administered at reperfusion, may also involve JAK/STAT signaling. (physiology.org)
  • In addition, in the light of a recent report that STAT3 is present in mitochondria and is required for optimal function of the electron transport chain and, hence, mitochondrial respiration ( 32 ), we considered the possibility that leptin-induced protection mediated via the JAK/STAT pathway is linked to MPTP function. (physiology.org)
  • Leptin can regulate bone mass through a central, neuroendocrine signaling pathway. (jax.org)
  • In this study, we cloned the full-length open reading frame (ORF) of the leptin-a gene in the orange-spotted grouper, searched for polymorphisms, and performed association analyses between these polymorphisms and seven growth traits. (mdpi.com)
  • Our results demonstrate that several polymorphisms in the leptin-a gene are associated with growth traits and can be used for marker-assisted selection (MAS) in orange-spotted grouper populations. (mdpi.com)
  • To study factors associated with anemia and its effect on survival in HIV-infected persons treated with modern combined antiretroviral therapy (cART), we characterized the prevalence of anemia in the Veterans Aging Cohort Study (VACS) and used a candidate gene approach to identify proinflammatory gene single nucleotide polymorphisms (SNPs) associated with anemia in HIV disease. (epfl.ch)
  • Cannabinoid type 1 receptor gene polymorphisms are not associated with olanzapine-induced weight gain. (semanticscholar.org)
  • Detection of polymorphisms in the bovine leptin (LEP) gene: association of single nucleotide polymorphism with breeding value of milk traits in Iranian Holstein Cattle. (ijabbr.com)
  • Associations between leptin gene polymorphisms and production, live weight, energy balance, feed intake, and fertility in Holstein heifers. (ijabbr.com)
  • Genotype x nutrient association of common polymorphisms in obesity-related genes with food preferences and time structure of energy intake. (qxmd.com)
  • Potential association of leptin [LEP] gene polymorphisms has been suggested in the processes leading to breast cancer initiation and progression. (bvsalud.org)
  • Incubation of resting PBMCs with high-dose leptin (250 ng/ml, 3-5 days) induced proliferation of resting cultured PBMCs and their secretion of TNF-α (5-fold), IL-6 (19-fold), and IFN-γ (2.5-fold), but had no effect on IL-4 secretion. (jimmunol.org)
  • In fact, the fat content of a meal and habitual dietary fat content, but not carbohydrate or protein intake, are important factors that can modify leptin secretion (11-13). (scielo.br)
  • This relation was not seen in depressed patients, suggesting a disturbed regulation of leptin secretion in mood disorders (10). (scielo.br)
  • In fact, these patients present more intense leptin secretion during the night when compared to normal subjects, despite a reported weight loss by the majority of patients (10). (scielo.br)
  • Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. (nih.gov)
  • It binds to the leptin receptor (Ob-R) which is expressed as several different isoforms [ 8 ]. (medsci.org)
  • Our study provides novel insight into the association between genetic variability in the leptin gene and anemia in HIV+ individuals. (epfl.ch)
  • DISCUSSION: To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. (lancs.ac.uk)
  • Rodents with genetic abnormalities in leptin and leptin receptor expression have deficits in macrophage phagocytosis and endotoxin-mediated induction of TNF-α and IL-6 ( 12 ). (jimmunol.org)
  • New Genes IDd in Obesity: How Much of Weight is Genetic? (beliefnet.com)
  • Objective: Identity the genetic aspects and major gene influence on energy balance, milk production, fertility, food safety and consumer are the recent interests of genetic and breeding researchers. (ijabbr.com)
  • The present study revealed that allelic association at ApoB, LPL, Leptin loci and loss of telomere length may have strong genetic association with hypertensive individuals. (beds.ac.uk)
  • We investigated whether genetic variations in the LEP -2548G/ A gene are associated with risk of breast cancer . (bvsalud.org)
  • Though further research is warranted to determine whether leptin gene therapy would be safe and effective for humans, the team believes their findings suggest it may be a promising strategy against obesity - one that does not have negative implications for bone health. (medicalnewstoday.com)
  • A similar phenotype is observed in the case of leptin-deficient humans. (biomedcentral.com)
  • However, leptin administration to leptin-sufficient humans at usual body weight has little or no effect on weight unless given in doses 10-20 times what would be considered to be in the normal physiological range. (clinicaltrials.gov)
  • Leptin expert Dr Elif A Oral (University of Michigan, Ann Arbor) told Medscape Medical News , "As far as I know, this is the first report of biologically inactive leptin seen in humans per se, but there have been reports of most of the other peptide hormones having inactive mutants. (medscape.com)