Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9BY76 (adipokine)
 3,147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the source of adipokines released by the visceral and sc adipose tissues of obese humans. Human adipose tissue incubated in primary culture for 48 h released more prostaglandin E(2), IL-8, and IL-6 than adiponectin, whereas the release of plasminogen activator inhibitor 1 and hepatocyte growth factor was less than that of adiponectin but greater than that of leptin. IL-10 and TNFalpha were released in amounts less than those of leptin, whereas vascular endothelial growth factor and IL1-beta were released in much lower amounts. The accumulation of adipokines was also examined in the three fractions (adipose tissue matrix, isolated stromovascular cells, and adipocytes) obtained by collagenase digestion of adipose tissue. Over 90% of the adipokine release by adipose tissue, except for adiponectin and leptin, could be attributed to nonfat cells. Visceral adipose tissue released greater amounts of vascular endothelial growth factor, IL-6, and plasminogen activator inhibitor 1 compared with abdominal sc tissue. The greatly enhanced total release of TNFalpha, IL-8, and IL-10 by adipose tissue from individuals with a body mass index of 45 compared with 32 was due to nonfat cells. Furthermore, most of the adipokine release by the nonfat cells of adipose tissue was due to cells retained in the tissue matrix after collagenase digestion.
 ...
PMID:Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. 1472 44

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.
 ...
PMID:Adipokines: inflammation and the pleiotropic role of white adipose tissue. 1546 38

Adiponectin is the abundant adipocyte-derived protein with well-established anti-atherogenic and insulin-sensitising properties. Besides these well characterised biological functions, recent evidence supports a strong anti-inflammatory function. Whereas initial studies demonstrated that adiponectin suppresses the production of the potent pro-inflammatory cytokine TNF-alpha, current studies showed that this adipokine also induces various anti-inflammatory cytokines, such as IL-10 or -1 receptor antagonists. These effects are paralleled by various other immune-regulatory properties, such as specific effects on endothelial cell functions. These in vitro effects are directly translated into various animal models of inflammation, demonstrating a potent anti-inflammatory effect for adiponectin. Thiazolidinediones selectively upregulate peroxisome-proliferator-activated receptor-gamma, leading to increased tissue and serum concentrations of adiponectin. Adiponectin has emerged as a key mediator regulating and affecting the balance between fat and inflammation. Therefore, either adiponectin itself or its inducing agents, such as thiazolidinediones, might be of key therapeutic interest in the near future far beyond diseases being associated with insulin resistance.
 ...
PMID:Adiponectin: a key fat-derived molecule regulating inflammation. 1593 13

Adipose tissue has been recognised as the quantitatively most important energy store of the human body for many years, in addition to its functions as mechanical and thermic insulator. In mammals, the adipose organ is localised in several depots including white as well as brown adipose tissues. The largest depots are found subcutaneously and in the abdominal region. Several secretory proteins are synthesised in adipose tissue including leptin, resistin, adiponectin, tumor necrosis factor (TNFalpha), angiotensinogen, adipsin, acylation-stimulating protein, retinol-binding protein (RBP), interleukin (IL)-1b, IL-6, IL-8, IL-10, plasminogen activator inhibitor-1 (PAI-1), fasting-induced adipose factor, fibrinogen-angiopoietin-related protein, metallothionein, tissue factor (TF), complement C3, fibronectin, haptoglobin, entactin/nidogen, collagen VI alpha 3, pigment epithelium-derived factor (PEDF), hippocampal cholinergic neurostimulating peptide (HCNP), neutrophil gelatinase-associated lipocalin (NGAL) and adiponutrin. Fatty acids may influence the expression of adipokines like leptin, resistin or adiponectin directly by interaction with transcription factors, or indirectly via unknown mechanisms possibly linked to fatty acid oxidation, synthesis or storage. Because fatty acids are the main components of adipose tissue, it is of essential interest to clarify the biological effects of different types of fatty acids on the expression of relevant adipokines.
 ...
PMID:Fatty acids and expression of adipokines. 1594 95

White adipose tissue (WAT) is now recognized as a major endocrine and secretory organ, releasing a wide range of protein factors and signals termed adipokines - in addition to fatty acids and other lipid moieties. A paradigm shift came with the discovery of leptin, a pleiotropic hormone which is a critical signal to the hypothalamus in the control of appetite and energy balance. A number of adipokines, including adiponectin, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor-1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of mild inflammation, and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands; a notable exception is adiponectin, with its anti-inflammatory action, the levels of which fall. WAT may be the main site of inflammation in obesity, increased circulating levels of inflammatory markers reflecting spillover from an 'inflamed' tissue, leading to the obesity-associated pathologies of type 2 diabetes and the metabolic syndrome. From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems. Whether major changes in adipokine production in obesity, particularly of those factors linked to inflammation, are unique to this condition, or are a feature of all situations in which there are substantial increases in adipose mass (such as pregnancy, and pre-hibernatory and pre-migratory fattening) requires consideration.
 ...
PMID:Endocrine and signalling role of adipose tissue: new perspectives on fat. 1602 20

Adiponectin (APM) is an adipocyte-derived adipokine with immunosuppressive, antidiabetic, and antiatherosclerotic properties. Low molecular weight (LMW)- and higher molecular weight (HMW)-APM circulate in the serum and activate different signaling pathways. We were interested to see whether LMW-APM exerts different effects on monocytic cells compared with the HMW isoform. Therefore, the effects of recombinant LMW-APM produced in insect cells and the APM from higher eukaryotic cells containing HMW forms on monocytic cells were investigated with respect to apoptosis and inflammation. LMW- and HMW-APM induce apoptosis in nondifferentiated THP-1 cells, reduce macrophage scavenger receptor (MSR) A mRNA expression, and stimulate phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). However, HMW-APM induces the secretion of interleukin (IL)-6 in human monocytes and THP-1 cells but does not suppress lipopolysaccharide (LPS)-induced IL-6 secretion. In contrast, LMW-APM reduces LPS-mediated IL-6 release and furthermore, stimulates IL-10 secretion, most likely by reducing the abundance of inhibitor of nuclear factor (NF)-kappaB kinase beta, leading to a diminished nuclear translocation of NF-kappaB p65. Our data indicate that the different APM isoforms do share common effects on monocytic cells but also induce isoform-specific responses. Although apoptosis, the activation of AMPK, and the reduction of MSR are mediated by all APM isoforms, only LMW-APM displays anti-inflammatory properties.
 ...
PMID:Different effects of adiponectin isoforms in human monocytic cells. 1643 92

Angiopoietin-like protein 4 (Angptl4)/FIAF (fasting-induced adipose factor) was first identified as a target for PPAR and to be strongly induced in white adipose tissue (WAT) by fasting. Here we have examined the regulation of the expression and release of this adipokine in mouse WAT and in 3T3-L1 adipocytes. Angptl4/FIAF expression was measured by RT-PCR and real-time PCR; plasma Angptl4/FIAF and release of the protein in cell culture was determined by western blotting. The Angptl4/FIAF gene was expressed in each of the major WAT depots of mice, the mRNA level in WAT being similar to the liver and much higher (>50-fold) than skeletal muscle. Fasting mice (18 h) resulted in a substantial increase in Angptl4/FIAF mRNA in liver and muscle (9.5- and 21-fold, respectively); however, there was no effect of fasting on Angptl4/FIAF mRNA in WAT and the plasma level of Angptl4/FIAF was unchanged. The Angptl4/FIAF gene was expressed in 3T3-L1 adipocytes before and after differentiation, the level increasing post-differentiation; Angptl4/FIAF was released into the culture medium. Insulin, leptin, dexamethasone, noradrenaline, TNFalpha and several IL (IL-1beta, IL-6, IL-10, IL-18) had little effect on Angptl4/FIAF mRNA levels in 3T3-L1 adipocytes. However, a major stimulation of Angptl4/FIAF expression was observed with rosiglitazone and the inflammatory prostaglandins PGD2 and PGJ2. Angptl4/FIAF does not act as an adipose tissue signal of nutritional status, but is markedly induced by fasting in liver and skeletal muscle.
 ...
PMID:Regulation of angiopoietin-like protein 4/fasting-induced adipose factor (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3-L1 adipocytes. 1808 44

Adiponectin is an adipokine with potent anti-inflammatory properties. The development of alcoholic liver disease is thought to involve increased pro-inflammatory activity, mediated in part by the activation of hepatic macrophages (Kupffer cells). Chronic ethanol feeding sensitizes hepatic macrophages to activation by lipopolysaccharide (LPS), leading to increased production of reactive oxygen species and tumor necrosis factor-alpha (TNF-alpha). Adiponectin can normalize Toll-like receptor-4 (TLR-4) mediated signaling in hepatic macrophages after ethanol feeding, likely contributing to the hepatoprotective effect of adiponectin in the progression of alcoholic liver disease. However, the mechanisms by which adiponectin suppress TLR-4 mediated responses are not well understood. Using the macrophage-like cell line, RAW264.7, we have investigated the molecular mechanisms by which adiponectin suppresses LPS-stimulated TNF-alpha production. Globular adiponectin (gAcrp)-mediated desensitization of LPS-stimulated responses in RAW264.7 macrophages was dependent on the production of the anti-inflammatory cytokine interleukin (IL)-10. gAcrp initially increased TNF-alpha expression in RAW264.7 macrophages; this TNF-alpha then contributed to increased expression of IL-10. This initial gAcrp-mediated increase in TNF-alpha production by macrophages was mediated via activation of ERK1/2-->Egr-1 and nuclear factor (NF)-kappaB-dependent mechanisms. gAcrp-stimulated IL-10 expression was also dependent on the phosphorylation of cAMP response element-binding protein and the cAMP response element in the IL-10 promoter. In summary, these studies reveal a complex, integrated response of macrophages to gAcrp. gAcrp initially activated signaling pathways considered to be pro-inflammatory, with a subsequent increase in the expression of the potent, anti-inflammatory cytokine, IL-10. Increased IL-10 expression was ultimately required for the suppression of TLR4-mediated signaling by gAcrp.
 ...
PMID:Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. 1833 64

This study examined ontogeny of development for a range of adipokines in neonatal adipose tissue. Pigs (Sus scrofa) were selected across six litters for sampling subcutaneous (SQ) and perirenal (PR) adipose tissues at d1, d4, d7 or d21 of age and total RNA extraction. Reverse transcription and real-time PCR were used to quantify mRNA abundance for: leptin, adiponectin, interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, IL-15, tumor necrosis factor alpha (TNFalpha), haptoglobin, vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein 1 (MCP1) and cyclophilin. Leptin, adiponectin and IL-15 expression increased from d1 to d 21 of age in both SQ and PR. Haptoglobin, VEGF, MIF and IL-8 expression decreased between d1 and d4 of age in SQ. TNFalpha expression was unchanged from d1-7 and then increased at d21. IL-1beta, IL-6 and IL-10 expression were unchanged with age in SQ; whereas IL-1beta and IL-6 mRNA abundance in the PR increased with age. Analysis of the mRNA abundance for these adipokines within adipose tissue from d1 to d21 of age demonstrated that neonatal development of adipokine expression varies among the different adipokines and the internal and external sites of adipose tissue deposition (PR versus SQ).
 ...
PMID:Ontogeny of adipokine expression in neonatal pig adipose tissue. 1893 Aug 35

The goal of this study was to investigate the role of the adipokine adiponectin (APN) in development of spontaneous colitis in IL-10 knockout (KO) mice. To this aim, we generated double IL-10 APN KO mice and compared their disease development to that of single IL-10 KO mice. Both IL-10 KO and double IL-10 APN KO mice spontaneously developed colitis of comparable severity. No significant differences in inflammatory infiltrate or crypt elongation were observed in colonic tissue obtained from IL-10 KO and double IL-10 APN KO mice at either 12 or 20 wk of age. A comparable increase in circulating levels of serum amyloid A and IFN-gamma was observed in IL-10 KO and double IL-10 APN KO mice as disease progressed. In vitro stimulation of lymphocytes from mesenteric lymph nodes with anti-CD3 and anti-CD28 induced a significantly higher production of IL-17 and TNF-alpha in IL-10 KO and double IL-10 APN KO mice compared with their healthy littermates. No significant differences in cytokine production from lymphocytes or colonic mRNA expression of cytokines were observed between IL-10 KO and double IL-10 APN KO mice. Both IL-10 KO and double IL-10 APN KO mice had a similar decrease in body weight and bone mass compared with their respective healthy littermates. Finally, APN deficiency did not lead to development of insulin resistance, either in APN KO or double IL-10 APN KO mice. In conclusion, lack of APN does not play a significant role in the pathogenesis of spontaneous colonic inflammation in the IL-10 KO model.
 ...
PMID:Adiponectin deficiency does not affect development and progression of spontaneous colitis in IL-10 knockout mice. 1907 37


1 2 3 4 5 Next >>