Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ
01 Aug 2001-Vol. 60, Iss: 3, pp 329-339
TL;DR: The key challenges in establishing the secretory functions of white fat are to identify the complement of secreted proteins, to establish the role of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production with alterations in adiposity.
Abstract: The traditional role attributed to white adipose tissue is energy storage, fatty acids being released when fuel is required. The metabolic role of white fat is, however, complex. For example, the tissue is needed for normal glucose homeostasis and a role in inflammatory processes has been proposed. A radical change in perspective followed the discovery of leptin; this critical hormone in energy balance is produced principally by white fat, giving the tissue an endocrine function. Leptin is one of a number of proteins secreted from white adipocytes, which include angiotensinogen, adipsin, acylation-stimulating protein, adiponectin, retinol-binding protein, tumour neorosis factor a, interleukin 6, plasminogen activator inhibitor-1 and tissue factor. Some of these proteins are inflammatory cytokines, some play a role in lipid metabolism, while others are involved in vascular haemostasis or the complement system. The effects of specific proteins maybe autocrine or paracrine, or the site of action maybe distant from adipose tissue. The most recently described adipocyte secretory proteins are fasting-induced adipose factor, a fibrinogen-angiopoietin-related protein, metallothionein and resistin. Resistin is an adipose tissue-specific factor which is reported to induce insulin resistance, linking diabetes to obesity. Metallothionein is a metal-binding and stress-response protein which may have an antioxidant role. The key challenges in establishing the secretory functions of white fat are to identify the complement of secreted proteins, to establish the role of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production with alterations in adiposity (obesity, fasting, cachexia). There is already considerable evidence of links between increased production of some adipocyte factors and the metabolic and cardiovascular complications of obesity. In essence, white adipose tissue is a major secretory and endocrine organ involved in a range of functions beyond simple fat storage.
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TL;DR: Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.
Abstract: The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.
3,281 citations
TL;DR: It is suggested that the term ‘adipokine’ be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue.
Abstract: 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.
2,163 citations
Cites background from "Physiological role of adipose tissu..."
...This is in addition to the adipocytes’ central role in the deposition and release of fatty acids (Mohamed-Ali et al. 1998; Frühbeck et al. 2001; Trayhurn & Beattie, 2001)....
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...2), both in terms of protein structure and of putative function, is considerable (Frühbeck et al. 2001; Trayhurn & Beattie, 2001)....
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...However, one hypothesis would be that the various factors may relate ultimately to the central lipid storage and release function of the tissue (Trayhurn & Beattie, 2001)....
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TL;DR: This document is the first update of the American College of Gastroenterology (ACG) colorectal cancer screening recommendations since 2000, and it is recognized that colonoscopy is not available in every clinical setting because of economic limitations.
1,409 citations
TL;DR: The authors used the method of instrumental variables (IV) to estimate the impact of obesity on medical costs in order to address the endogeneity of weight and to reduce the bias from reporting error in weight.
1,329 citations
TL;DR: The ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponECTin levels.
Abstract: Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.
1,142 citations
Cites background from "Physiological role of adipose tissu..."
...Adipose tissue is currently considered as a hormonally active system in the control of metabolism and not only as a store of excess energy ( 1 )....
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References
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TL;DR: The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.
Abstract: The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation of ob results in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.
12,394 citations
"Physiological role of adipose tissu..." refers background in this paper
...Leptin (also termed OB protein) was discovered in 1994 by Friedman and colleagues (Zhang et al. 1994), with the identification of the mutant gene which underlies the development of the obesity of the ob/ob mouse....
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...The leptin gene (Lep(ob)) encodes a protein of molecular weight 18 000 containing a signal sequence which is cleaved to produce the mature hormone of molecular weight 16 000 (Zhang et al. 1994)....
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...The critical change in our perspectives on WAT came with the discovery of the cytokine-like factor, leptin (Zhang et al. 1994)....
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TL;DR: A role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity is indicated.
Abstract: Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
7,347 citations
"Physiological role of adipose tissu..." refers background in this paper
...TNF-α production is increased in obesity, and the cytokine has been implicated in the development of insulin resistance in the adipocyte of the obese by altering insulin signalling through an autocrine or paracrine action (Hotamisligil et al. 1993; Hotamisligil, 2000)....
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TL;DR: Serum leptin concentrations are correlated with the percentage of body fat, suggesting that most obese persons are insensitive to endogenous leptin production.
Abstract: Background Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese and lose weight when given leptin, but little is known about the physiologic actions of leptin in humans. Methods Using a newly developed radioimmunoassay, we measured serum concentrations of leptin in 136 normal-weight subjects and 139 obese subjects (body-mass index, >27.3 for men and >27.8 for women; the body-mass index was defined as the weight in kilograms divided by the square of the height in meters). The measurements were repeated in seven obese subjects after weight loss and during maintenance of the lower weight. The ob messenger RNA (mRNA) content of adipocytes was determined in 27 normal-weight and 27 obese subjects. Results The mean (±SD) serum leptin concentrations were 31.3±24.1 ng per milliliter in the obese subjects and 7.5±9.3 ng per milliliter in the normal-weight subjects (P<0.001). There was a strong positive correlation between serum leptin concentration...
6,350 citations
"Physiological role of adipose tissu..." refers background in this paper
...This fact is evident from the correlation between plasma leptin and indices of body fatness in both human subjects and experimental animals (Considine et al. 1996; Ostlund et al. 1996)....
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TL;DR: The role of leptin in the control of body weight and its relevance to the pathogenesis of obesity are reviewed.
Abstract: The assimilation, storage and use of energy from nutrients constitute a homeostatic system that is essential for life In vertebrates, the ability to store sufficient quantities of energy-dense triglyceride in adipose tissue allows survival during the frequent periods of food deprivation encountered during evolution However, the presence of excess adipose tissue can be maladaptive A complex physiological system has evolved to regulate fuel stores and energy balance at an optimum level Leptin, a hormone secreted by adipose tissue, and its receptor are integral components of this system Leptin also signals nutritional status to several other physiological systems and modulates their function Here we review the role of leptin in the control of body weight and its relevance to the pathogenesis of obesity
5,335 citations
"Physiological role of adipose tissu..." refers background in this paper
...The hormone, which is widely viewed as the most important protein factor secreted by WAT, has been extensively reviewed (see Friedman & Halaas, 1998; Trayhurn et al. 1999; Ahima et al. 2000; Harris, 2000), and it is therefore our intention to summarise here only the central elements of its biology,…...
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TL;DR: Plasma concentrations of adiponectin in obese subjects were significantly lower than those in non-obese subjects, although adip onectin is secreted only from adipose tissue.
4,882 citations
"Physiological role of adipose tissu..." refers background in this paper
...In contrast to many proteins secreted by adipose tissue, expression of the adiponectin gene and the circulating level of the protein fall in obesity (Arita et al. 1999) and in diabetes (Hotta et al. 2000)....
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...In contrast to many proteins secreted by adipose tissue, expression of the adiponectin gene and the circulating level of the protein fall in obesity (Arita et al. 1999) and in diabetes (Hotta et al....
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