The role of adipose tissue as an endocrine gland (original) (raw)
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Pro-inflammatory cytokines and adipose tissue
Proceedings of the Nutrition Society, 2001
Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor a (TNF-a) and several interleukins (IL), notably IL-1b and IL-6. Other adipocyte products with ‘immunological’ actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-a and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-a mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual ‘inflammatory‘ stimuli such as lipopolysaccaride, but a...
American Journal of Physiology-Endocrinology and Metabolism, 2003
Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-α). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-α on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% ( P < 0.05) increase in plasma adiponectin and a 45% ( P < 0.05...
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-α, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.
Nutrition & Diabetes, 2017
The importance of the involvement of adipose tissue macrophage subpopulations in obesity-related disorders is well known from different animal models, but human data are scarcer. Subcutaneous (n = 44) and visceral (n = 52) adipose tissues of healthy living kidney donors were obtained during living donor nephrectomy. Stromal vascular fractions were isolated and analysed by flow cytometry using CD14, CD16, CD36 and CD163 antibodies. Total macrophage numbers in subcutaneous adipose tissue increased (P = 0.02) with body mass index (BMI), with a similar increase seen in the proportion of phagocytic CD14+CD16+CD36 high macrophages (P o0.01). On the other hand, there was an inverse correlation between anti-inflammatory CD14+CD16 − CD163+ macrophages (P o0.05) and BMI. These correlations disappeared after excluding obese subjects (BMI ⩾ 30 kg m − 2) from the analysis. Interestingly, none of these subpopulations were significantly related to BMI in visceral adipose tissue. Obesity per se is associated with distinct, highly phagocytic macrophage accumulation in human subcutaneous adipose tissue.
Peripheral Factors in the Metabolic Syndrome: The Pivotal Role of Adiponectin
Annals of The New York Academy of Sciences, 2006
Abstract: Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and prostaglandin E2 (PGE2). We have previously shown that adiponectin is a powerful inducer of proinflammatory cytokines production by macrophages. The reported anti-inflammatory effect of adiponectin may be due to the induction of macrophage tolerance to further adiponectin exposure or to other proinflammatory stimuli including the Toll-like receptor (TLR) 3 ligand polyI:C and the TLR4 ligand lipopolysaccharide (LPS). We now present additional data supporting the hypothesis that adiponectin is a strong proinflammatory adipokine. More specifically, we demonstrate that adiponectin induces IL-1β and IL-8 from THP-1 macrophage cell line. The effect of adiponectin is not restricted to differentiated THP-1 macrophages but it is evident at lower levels in undifferentiated THP-1 monocytes promoting TNF-α, IL-6, and IL-8 production. Thus, its high levels in the circulation of lean subjects render their macrophages resistant to several proinflammatory stimuli including its own thus acting in effect as an anti-inflammatory agent. Lowering of its high levels, as a consequence of increased body mass index (BMI), renders macrophages sensitive to any proinflammatory insult.
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj Napoca Veterinary Medicine, 2008
BACKGROUND Obesity, with all its comorbidities, is increasingly recognized as a major health problem (1). Recent literature indicates a link between the process of fat formation and inflammation (2,3). Obesity, alone or as a part of the metabolic syndrome, is characterized by a state of chronic low-level inflammation as revealed by raised plasma levels of inflammatory cytokines and acute-phase proteins. When adipocytes increase in size during weight-gain, they secrete tumor necrosis factor (TNF-α), which, in turn, stimulates monocyte chemoattractant protein MCP-1 release. MCP-1 recruits monocytes from the circulation, which infiltrate adipose tissue and stimulate adipocytes to produce the inflammatory cytokines (1). The altered production of pro inflammatory molecules (so-called "adipokines") by adipose tissue has been implicated in the metabolic complications of obesity. Compared with adipose tissue of lean individuals, adipose tissue of the obese expresses increased amounts of pro inflammatory proteins such as TNF-α, IL-6, iNOS (also known as NOS2), TGF-β1, C-reactive protein, soluble ICAM, and monocyte chemotactic protein-1 (MCP-1) and procoagulant proteins such as plasminogen activator inhibitor type-1 (PAI-1), tissue factor, and factor VII. That adipocytes express receptors for several pro inflammatory molecules (e.g., TNF-α, IL-6) supports models in which adipocytes were both the source and target of pro inflammatory signals (4). Obesity induces adipose tissue macrophage infiltration in both humans and mice (5). Macrophage numbers and/or macrophage inflammatory gene expression in white adipose tissue are positively correlated with adipocyte size and body mass index (BMI) in mice and negatively correlated with weight loss in obese humans (4). Macrophages are the predominant source of tumor necrosis factor-(TNF-) and a significant source of interleukin-6 and nitric oxide in white adipose tissue of obese (ob/ob, db/db) mice and humans (4,6). A "spike" in macrophage inflammatory gene expression in white adipose tissue immediately precedes or is coincident with the onset of hyperinsulinemia in murine dietinduced obesity. These observations implicate macrophage activation in the development of obesity associated white adipose tissue inflammation and insulin resistance (7). Chronic inflammation and angiogenesis are two processes that assemble together. These two phenomena have long been coupled together in many chronic inflammatory disorders with distinct etiopathogenic origin, including psoriasis, rheumatoid arthritis, Crohn's disease, diabetes, and cancer. Lately, this concept has further been substantiated by the
Obesity, 2005
DEGAWA-YAMAUCHI, MIKAKO. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor ␣. Obes Res. 2005;13:662-669. Objective: Adiponectin mRNA expression in isolated subcutaneous and omental adipocytes was examined across a wide range of adiposity to determine whether adiponectin synthesis is impaired in these adipose tissue depots in obese humans. Tumor necrosis factor (TNF)␣ and dexamethasone were tested for inhibitory effects on adiponectin release from human adipocytes in vitro.
Adipocytokines: The pied pipers
Journal of Pharmacology and Pharmacotherapeutics, 2010
Even though there have been major advances in therapy, atherosclerosis and coronary artery disease retain their lead as one of the major causes of morbidity and mortality in the fi rst decade of 21 st century. To add to the woes, we have diabetes, obesity and insulin resistance as the other causes. The adipose tissue secretes several bioactive mediators that infl uence infl ammation, insulin resistance, diabetes, atherosclerosis and several other pathologic states besides the regulation of body weight. These mediators are mostly proteins and are termed "adipocytokines". Adiponectin, resistin, visfatin, retinol binding protein-4 (RBP-4) and leptin are a few such proteins. Adiponectin is a multimeric protein, acting via its identifi ed receptors, AdipoR1 and AdipoR2. It is a potential biomarker for metabolic syndrome and has several antiinfl ammatory actions. Adiponectin increases insulin sensitivity and ameliorates obesity. Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance. It plays a role in the pathophysiology of several conditions because of its robust proinfl ammatory activity mediated through the activation of extracellular signal regulated kinases 1 and 2 (ERK 1/2). In 2007, resistin was reported to have protective effect in ischemia-reperfusion injury and myocyte-apoptosis in the setting of myocardial infarction (MI). RBP-4 is involved in the developmental pathology of type 2 diabetes mellitus and obesity. Visfatin has been described as an infl ammatory cytokine. Increased expression of visfatin mRNA has been observed in infl ammatory conditions like atherosclerosis and infl ammatory bowel disease. Leptin mainly regulates the food intake and energy homeostasis. Leptin resistance has been associated with development of obesity and insulin resistance. Few drugs (thiazolidinediones, rimonabant, statins, etc.) and some lifestyle modifi cations have been found to improve the levels of adipocytokines. Their role in therapy has a lot in store to be explored upon.