Resistin
Hormones, Ectopic
Adiponectin
Adipokines
Leptin
Insulin Resistance
Adipocytes
Nerve Growth Factor
Intercellular Signaling Peptides and Proteins
3T3-L1 Cells
Insulin
A family of tissue-specific resistin-like molecules. (1/446)
We have identified a family of resistin-like molecules (RELMs) in rodents and humans. Resistin is a hormone produced by fat cells. RELMalpha is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue. Another family member, RELMbeta, is a secreted protein expressed only in the gastrointestinal tract, particularly the colon, in both mouse and human. RELMbeta gene expression is highest in proliferative epithelial cells and is markedly increased in tumors, suggesting a role in intestinal proliferation. Resistin and the RELMs share a cysteine composition and other signature features. Thus, the RELMs together with resistin comprise a class of tissue-specific signaling molecules. (+info)A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. (2/446)
A 12.5-kDa cysteine-rich adipose tissue-specific secretory factor (ADSF/resistin) is a novel secreted protein rich in serine and cysteine residues with a unique cysteine repeat motif of CX(12)CX(8)CXCX(3)CX(10)CXCXCX(9)CC. A single 0.8-kilobase mRNA coding for this protein was found in various murine white adipose tissues including inguinal and epididymal fats and also in brown adipose tissue but not in any other tissues examined. Two species of mRNAs with sizes of 1.4 and 0.8 kilobases were found in rat adipose tissue. Sequence analysis indicates that this is because of two polyadenylation signals, the proximal one with the sequence AATACA with a single base mismatch from murine AATAAA and the distal consensus sequence AATAAA. The mRNA level was markedly increased during 3T3-L1 and primary preadipocyte differentiation into adipocytes. Its expression in adipose tissue is under tight nutritional and hormonal regulation; the mRNA level was very low during fasting and increased 25-fold when fasted mice were refed a high carbohydrate diet. It was also very low in adipose tissue of streptozotocin-diabetes and increased 23-fold upon insulin administration. Upon treatment with the conditioned medium from COS cells transfected with the expression vector, conversion of 3T3-L1 cells to adipocytes was inhibited by 80%. The regulated expression pattern suggesting this factor as an adipose sensor for the nutritional state of the animals and the inhibitory effect on adipocyte differentiation implicate its function as a feedback regulator of adipogenesis. (+info)Dimerization of resistin and resistin-like molecules is determined by a single cysteine. (3/446)
Resistin is a peptide hormone secreted by adipocytes. Cysteine residues comprise 11 of 94 (12%) amino acids in resistin. The arrangement of these cysteines is unique to resistin and its recently discovered family of tissue-specific secreted proteins, which have been independently termed resistin-like molecules (RELMs) and the FIZZ (found in inflammatory zone) family. Here we show that resistin is a disulfide-linked homodimer that can be converted to a monomer by reducing conditions. The intestine-specific RELM beta has similar characteristics. Remarkably, however, the adipose-enriched RELM alpha is a monomer under non-reducing conditions. We note that RELM alpha lacks a cysteine residue, closest to the cleaved N terminus, that is present in resistin and RELM beta in multiple species. Conversion of this cysteine to alanine abolishes dimerization of resistin. Thus, a single disulfide bond is necessary to connect two resistin subunits in a homodimer. The additional 10 cysteines most likely participate in intramolecular disulfide bonds that define the conserved structure of the family members. The monomeric nature of RELM alpha suggests structural and potentially functional divergence between resistin and this close family member. (+info)Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. (4/446)
Elevated levels of the hormone resistin, which is secreted by fat cells, are proposed to cause insulin resistance and to serve as a link between obesity and type 2 diabetes. In this report we show that resistin expression is significantly decreased in the white adipose tissue of several different models of obesity including the ob/ob, db/db, tub/tub, and KKA(y) mice compared with their lean counterparts. Furthermore, in response to several different classes of antidiabetic peroxisome proliferator-activated receptor gamma agonists, adipose tissue resistin expression is increased in both ob/ob mice and Zucker diabetic fatty rats. These data demonstrate that experimental obesity in rodents is associated with severely defective resistin expression, and decreases in resistin expression are not required for the antidiabetic actions of peroxisome proliferator-activated receptor gamma agonists. (+info)Isoproterenol inhibits resistin gene expression through a G(S)-protein-coupled pathway in 3T3-L1 adipocytes. (5/446)
Resistin was recently identified as a hormone secreted by adipocytes which leads to insulin resistance in vivo and in vitro and might therefore be an important link between obesity and diabetes. To clarify the regulation of resistin gene expression, 3T3-L1 adipocytes were treated with various agents known to modulate insulin sensitivity, and resistin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, isoproterenol treatment reduced the level of resistin mRNA to 20% of non-treated control cells. This effect was dose-dependent with significant inhibition occurring at concentrations as low as 10 nM isoproterenol. Moreover, pretreatment of adipocytes with the beta-adrenergic antagonist propranolol almost completely reversed the inhibitory effect of isoproterenol, whereas addition of the alpha-adrenergic antagonist phentolamine did not have any effect. Furthermore, the effect of isoproterenol could be mimicked by activation of G(S)-proteins and adenylyl cyclase. Thus, both cholera toxin and forskolin decreased resistin mRNA expression in a dose-dependent fashion by up to 90% of control levels. Taken together, these results suggest that resistin gene expression is regulated by a protein kinase A-dependent pathway in 3T3-L1 adipocytes. (+info)Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. (6/446)
Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-gamma agonists markedly upregulated fatty acid-binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-gamma (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-gamma action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism. (+info)Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. (7/446)
Expression of the gene encoding resistin, a low molecular weight protein secreted from adipose tissue postulated to link obesity and type II diabetes, was examined in 3T3-L1 adipocytes. Resistin mRNA was detected in 3T3-L1 cells by day 3 following induction of differentiation into adipocytes; by day 4 the level of resistin mRNA peaked and remained high. The PPARgamma activators, rosiglitazone or darglitazone, reduced the level of resistin mRNA. Dexamethasone upregulated resistin mRNA level, but no effect was observed with the beta(3)-adrenoceptor agonist, BRL 37344. A substantial reduction in resistin mRNA level was observed with insulin, which induced decreases at physiological concentrations. Insulin may be a major inhibitor of resistin production, and this does not support a role for resistin in insulin resistance. (+info)Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels. (8/446)
The aim of this study was to investigate the regulation of resistin, a recently identified adipocyte-secreted peptide, in the adipose tissue of prolactin (PRL)-transgenic (tg) mice using ribonuclease protection assay. The level of resistin mRNA increased 3.5-fold in the adipose tissue of untreated male PRL-tg mice compared to controls. However, there was no difference in resistin expression in the adipose tissue of female PRL-tg mice compared to control mice. PRL-tg male mice have elevated serum testosterone levels and we therefore analyzed the effects of testosterone alone on resistin mRNA expression. Furthermore, the effects of elevated androgen levels on PRL receptor (PRLR) mRNA expression in the adipose tissue were investigated. Resistin mRNA increased 2.6-fold in the adipose tissue of control male mice with elevated serum androgen levels. In addition, PRLR mRNA expression was increased in the adipose tissue of male mice with elevated testosterone. These results suggest testosterone to be a regulator of resistin and PRLR mRNA expression in the adipose tissue of male mice. (+info)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.
Ectopic hormone production refers to the situation when a hormone is produced in an unusual location or by a type of cell that does not typically produce it. This can occur due to various reasons such as genetic mutations, cancer, or other medical conditions. The ectopic hormone production can lead to hormonal imbalances and related symptoms, as the regulation of hormones in the body becomes disrupted.
For example, in some cases of lung cancer, the tumor cells may produce adrenocorticotropic hormone (ACTH), which is typically produced by the pituitary gland. This ectopic ACTH production can result in Cushing's syndrome, a condition characterized by symptoms such as weight gain, muscle weakness, and high blood pressure.
It's important to note that ectopic hormone production is relatively rare and usually occurs in the context of specific medical conditions. If you suspect that you or someone else may have ectopic hormone production, it's important to seek medical attention from a healthcare professional who can provide appropriate evaluation and treatment.
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.
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.
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.
Insulin resistance is a condition in which the body's cells become less responsive to insulin, a hormone produced by the pancreas that regulates blood sugar levels. In response to this decreased sensitivity, the pancreas produces more insulin to help glucose enter the cells. However, over time, the pancreas may not be able to keep up with the increased demand for insulin, leading to high levels of glucose in the blood and potentially resulting in type 2 diabetes, prediabetes, or other health issues such as metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease. Insulin resistance is often associated with obesity, physical inactivity, and genetic factors.
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.
Nerve Growth Factor (NGF) is a small secreted protein that is involved in the growth, maintenance, and survival of certain neurons (nerve cells). It was the first neurotrophin to be discovered and is essential for the development and function of the nervous system. NGF binds to specific receptors on the surface of nerve cells and helps to promote their differentiation, axonal growth, and synaptic plasticity. Additionally, NGF has been implicated in various physiological processes such as inflammation, immune response, and wound healing. Deficiencies or excesses of NGF have been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, and pain conditions.
Intercellular signaling peptides and proteins are molecules that mediate communication and interaction between different cells in living organisms. They play crucial roles in various biological processes, including cell growth, differentiation, migration, and apoptosis (programmed cell death). These signals can be released into the extracellular space, where they bind to specific receptors on the target cell's surface, triggering intracellular signaling cascades that ultimately lead to a response.
Peptides are short chains of amino acids, while proteins are larger molecules made up of one or more polypeptide chains. Both can function as intercellular signaling molecules by acting as ligands for cell surface receptors or by being cleaved from larger precursor proteins and released into the extracellular space. Examples of intercellular signaling peptides and proteins include growth factors, cytokines, chemokines, hormones, neurotransmitters, and their respective receptors.
These molecules contribute to maintaining homeostasis within an organism by coordinating cellular activities across tissues and organs. Dysregulation of intercellular signaling pathways has been implicated in various diseases, such as cancer, autoimmune disorders, and neurodegenerative conditions. Therefore, understanding the mechanisms underlying intercellular signaling is essential for developing targeted therapies to treat these disorders.
3T3-L1 cells are a widely used cell line in biomedical research, particularly in the study of adipocytes (fat cells) and adipose tissue. These cells are derived from mouse embryo fibroblasts and have the ability to differentiate into adipocytes under specific culture conditions.
When 3T3-L1 cells are exposed to a cocktail of hormones and growth factors, they undergo a process called adipogenesis, during which they differentiate into mature adipocytes. These differentiated cells exhibit many characteristics of fat cells, including the accumulation of lipid droplets, expression of adipocyte-specific genes and proteins, and the ability to respond to hormones such as insulin.
Researchers use 3T3-L1 cells to study various aspects of adipocyte biology, including the regulation of fat metabolism, the development of obesity and related metabolic disorders, and the effects of drugs or other compounds on adipose tissue function. However, it is important to note that because these cells are derived from mice, they may not always behave exactly the same way as human adipocytes, so results obtained using 3T3-L1 cells must be validated in human cell lines or animal models before they can be applied to human health.
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.