Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

A variety of cytokines and other compounds are produced in the human adipose tissue and may have autocrine functions in the adipose tissue as well as be involved in the complications seen in association with obesity. Because it recently has been reported that interleukin 8 (IL-8), through its effects on the macrophage and endothelial cell, may be involved in the pathogenesis of atherosclerosis, we found it of interest to investigate whether IL-8 is produced in human adipose tissue in vitro. Human sc adipose tissue was investigated both in incubations with whole adipose tissue fragments as well as with isolated mature adipocytes. In adipose tissue fragments, IL-1beta (3 nM) and tumor necrosis factor alpha (0.6 nM) were able to stimulate IL-8 production by 12-fold and 5-fold, respectively (P < 0.001), when incubated for 48 h. Incubations with isolated adipocytes were performed up to 6 h, and IL-1beta and tumor necrosis factor alpha significantly increased IL-8 production by 50-60% (P < 0.05). Dexamethasone (50 nM) decreased IL-8 production from adipose tissue fragments by 57% (P < 0.01) and from adipocytes by 37% (P < 0.05). IL-8 messenger RNA expression in adipocytes incubated with IL-1beta was increased already after 2 h (P < 0.05). Thus, the effect of proinflammatory cytokines and dexamethasone on IL-8 production in adipose tissue seems to be mediated at the transcriptional level. In conclusion, it is demonstrated for the first time that IL-8 is produced and released from human adipose tissue and from isolated adipocytes in vitro, which may indicate that IL-8 from adipose tissue could be involved in some of the obesity-related complications.
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PMID:Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. 1123 19

Adipose tissue is not only a passive storage organ for excessed energy intake, it is also able to produce and release several substances with local (autocrine) and systemic (endocrine) actions. An up-to-date review of our knowledge in this area is given here. Several of the compounds deriving from adipose tissue have been shown to play a role in obesity-related health complications. The production of cytokines (TNF-alpha, IL-6, IL-8) is implicated in the development of insulin resistance and atherosclerosis. All elements in the renin-angiotensin system are produced in adipose tissue, which is thus related to hypertension. The production of PAI-1 could be related to enhanced thrombogenesis. The release of the compounds described is generally higher from adipocytes in the visceral depot, which could explain the close association between this depot and health complications.
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PMID:[Fatty tissue as a secretory organ. Significance for obesity-related diseases]. 1140 68

Obesity is associated with the increased risk of cardiovascular disease; however, mechanisms responsible for such an increase are not fully understood. IL-8 is a cytokine that might have atherogenic properties. Recent in vitro studies revealed that IL-8 is produced and secreted by human adipocytes. The aim of the present study was to evaluate plasma IL-8 concentrations in obese subjects and the relationships between circulating IL-8 and anthropometric and biochemical parameters and TNF-alpha system. A total of 75 subjects with normal glucose tolerance, 35 lean and 40 obese, were recruited for this study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test and after the euglycemic hyperinsulinemic clamp. A significant increase in plasma IL-8 was observed in the obese group. In simple regression analysis, performed for the initial evaluation of relationships, plasma IL-8 was related to body mass index, percentage of body fat, fat mass (FM), and soluble TNF-alpha receptor 2 (sTNFR2) in both groups and with waist-to-hip ratio and sTNFR1 in the obese. In multiple regression analysis, FM, waist-to-hip ratio, gender, sTNFR2, and low density lipoprotein cholesterol were responsible for 44% of IL-8 variability. During oral glucose tolerance testing, mean plasma IL-8 concentrations increased in both groups, whereas clamp resulted in a significant increase in plasma IL-8 only in the obese. We conclude that plasma IL-8 levels are increased in obese subjects, and are related to FM and TNF-alpha system. Increase in circulating IL-8 might be one of the factors linking obesity with greater cardiovascular risk.
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PMID:Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. 1236 41

IL-8 is released from human adipose tissue. Circulating IL-8 is increased in obese compared with lean subjects and is associated with measures of insulin resistance, development of atherosclerosis, and cardiovascular disease. We studied 1) the production and release of IL-8 in vitro from paired samples of subcutaneous (SAT) and visceral (VAT) adipose tissue and 2) the production of IL-8 from whole adipose tissue, isolated adipocytes, and nonfat cells of adipose tissue. IL-8 release from VAT was fourfold higher than from SAT (P < 0.05), and IL-8 mRNA was twofold higher in VAT compared with SAT (P < 0.01). Dexamethasone (50 nM) attenuated IL-8 production by 50% (P < 0.05), and IL-1beta (2 microg/l) increased IL-8 production up to 15-fold (P < 0.001). IL-8 release from whole SAT explants correlated with body mass index (BMI; r = 0.78; P < 0.001), as did IL-8 release from nonfat cells (r = 0.79; P < 0.001). However, no correlation was found between IL-8 release from the fraction of isolated adipocytes and BMI (r = 0.01). In conclusion, we demonstrated an increased release of IL-8 from VAT compared with SAT. Furthermore, our data suggest that the observed elevation in circulating levels of IL-8 in obese subjects is due primarily to the release of IL-8 from nonfat cells from adipose tissue. The high levels of IL-8 release from human adipose tissue and accumulation of this tissue in obese subjects may account for some of the increase in circulating IL-8 observed in obesity.
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PMID:Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. 1312 57

Adipokines such as Plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are elevated in patients with obesity, insulin resistance, and type 2 diabetes. In the present study, we investigated whether glucose affected the production of these adipokines in human adipose tissue in vitro. Glucose (up to 35mM) increased secretion of PAI-1 (p<0.01) and IL-8 (p<0.01), but not TNF-alpha, in a dose- and time-dependent manner. Half-maximal stimulatory concentration of glucose was about 1mM. Glucosamine (5mM) decreased production of PAI-1 (p<0.05) and IL-8 (p<0.05), indicating that the hexosamine biosynthesis pathway is not involved in the glucose-induced increment in adipokine secretion. The present data demonstrate that glucose increases PAI-1 and IL-8 secretion. However, glucose concentrations above 5mM had no additional effects on adipokine secretion, suggesting that mechanisms other than diabetes/insulin resistance-related hyperglycemia may be involved in the observed elevation of these adipokines.
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PMID:Stimulation of PAI-1 and adipokines by glucose in human adipose tissue in vitro. 1455 Feb 86

Numerous signals convey information about body fat status from the periphery to the brain areas that control energy homeostasis so that, throughout life, body weight remains nearly stable. These signals mainly originate, either from the adipose tissue, like leptin and to a lesser extent interleukin 6, or from the pancreas, like insulin and amylin. These factors circulate in proportion to body fat mass and they are referred to as "adiposity signals". It is well established, at least for leptin and insulin, that they enter the brain from the plasma where they induce/repress a network of important neuropeptide regulators of energy intake and expenditure. Beside these endocrine signals, a growing amount of literature show data relative to adipocyte-derived molecules, most of them belonging to the cytokine family, like IL6, TNFalpha, IL8, IL10 whose secretion also correlates with body fat mass and that may locally regulate fat mass expansion. Others, like adiponectin, are negatively correlated with body fat mass. These "adiposity molecules" have already been involved in insulin resistance associated with obesity and inflammatory process. They may participate to a complex inter organ dialogue. In this review, we will synthesize data relative to the role played by insulin, leptin and amylin, either alone or through a cross talk, in "energy level sensing" at the brain level. Furthermore, we will develop how "adiposity molecules" through their paracrin and/or autocrin action may contribute to maintain fat mass expansion, therefore representing new adiposity molecules per se. Lastly, since any distortion in the metabolic circuitry of energy homeostasis is susceptible to lead to a pathological status like obesity, the impact of known genetic polymorphisms in genes encoding the adiposity signals will be discussed.
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PMID:Adiposity signals, genetic and body weight regulation in humans. 1522 73

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.
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PMID:Adipokines: inflammation and the pleiotropic role of white adipose tissue. 1546 38

The present studies were designed to investigate the hormonal regulation of vascular endothelial growth factor (VEGF) release by human subcutaneous adipose tissue explants and adipocytes incubated in primary culture for 48 hours. Vascular endothelial growth factor and IL-8 release by adipocytes were less than 10% of that by tissue explants, whereas that of leptin in adipocytes was comparable to that by tissue. Dexamethasone inhibited VEGF formation by both adipose tissue explants and isolated adipocytes, whereas insulin stimulated VEGF release only in isolated adipocytes. Insulin also enhanced the formation of IL-8 and plasminogen activation inhibitor 1 (PAI-1), but not that of IL-6 by adipocytes although having little effect on that of IL-6 or PAI-1 by adipose tissue explants. Pertussis toxin stimulated lipolysis and inhibited leptin release by human adipose tissue or adipocytes but did not affect release of IL-8 or VEGF. Isoproterenol also stimulated lipolysis by human adipocytes, but this was not accompanied by any significant changes in VEGF, IL-8, IL-6, or PAI-1 release. In contrast, insulin stimulated VEGF release by human adipocytes, and this stimulation was enhanced in the presence of isoproterenol. Insulin stimulated VEGF formation as well as that of PAI-1 by human adipocytes, but not by explants under conditions where it had little effect on that of IL-6. The ability of insulin to stimulate VEGF formation by adipocytes suggests that the elevated circulating levels of insulin in obesity promote angiogenesis in adipose tissue as well as the enhanced accumulation of fat in human adipocytes.
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PMID:Insulin enhances vascular endothelial growth factor, interleukin-8, and plasminogen activator inhibitor 1 but not interleukin-6 release by human adipocytes. 1569 Mar 17

Obesity is characterized by an expanded adipose tissue mass. Recent data suggest that adipose tissue is a multi-functional organ rather than simply a passive storage site for excess energy. It has been clearly demonstrated that human adipose tissue produces a variety of secretory factors that exert multiple effects at both the local and the systemic level. To date, >100 products, covering a broad range of protein families as well as many fatty acids and prostaglandins, have been reported to be secreted by adipose tissue. The source of these secreted factors is not only mature fat cells but also poorly-identified cells present in the stromal-vascular fraction including macrophages. Secreted factors of particular interest include many cytokines or chemokines, such as TNF-alpha, IL-6, IL-8, as well as plasminogen activator inhibitor-1, angiotensin-II, leptin, and adiponectin. In the obese state the expression and secretion of these factors is disturbed. With the exception of adiponectin, most circulating factors are elevated. From this perspective, obesity can be described as a pro-inflammatory condition. In addition, regional differences in adipose expression of many of these factors have been found. There is now growing evidence that many secretory factors play an important role in the pathophysiology of the metabolic and cardiovascular complications of obesity. The question arising from these observations is how the secretory pattern of adipose tissue can be modified by dietary and pharmacological measures to reduce the health risks of obesity.
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PMID:Secretory factors from human adipose tissue and their functional role. 1596 Aug 61


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