Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications.
TL;DR: This chapter will review the phenotypic characteristics of different adipose depots and mechanisms that link their depot-specific biology to metabolic complications in men and women.
About: This article is published in Molecular Aspects of Medicine.The article was published on 2013-02-01 and is currently open access. It has received 634 citations till now. The article focuses on the topics: Adipose tissue & Adipokine.
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TL;DR: New perspective is gained on the roles played by adipocyte in a variety of homeostatic processes and on the mechanisms used by adipocytes to communicate with other tissues and how these relationships are altered during metabolic disease and how they might be manipulated to restore metabolic health.
1,746 citations
Cites background from "Adipose tissue heterogeneity: impli..."
...The most common classification scheme distinguishes between subcutaneous and visceral fat, in large part because the latter depot has a well-known association with metabolic disease, whereas the former does not (or may even be inversely correlated with disease risk) (Lee et al., 2013)....
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TL;DR: The metabolic syndrome is a multiplex risk factor for atherosclerotic cardiovascular disease and type 2 diabetes and at times, drug therapies or bariatric surgery may be required to control more overt risk factors.
570 citations
TL;DR: An overview of the role of adipose tissue in metabolic homeostasis is provided and emerging novel therapeutic strategies targeting adipOSE tissue are assessed, including adipokine-based strategies, promotion of white adiposa tissue beiging as well as reduction of inflammation and fibrosis.
Abstract: Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis.
502 citations
TL;DR: This Review consolidates the key information on the currently available animal models of obesity and diabetes and highlights the advantages, limitations and important caveats of each of these models.
Abstract: More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models.
500 citations
TL;DR: It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate withPPARγ to ensure adipocyte-specific genomic binding and function.
Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors (TFs) and function as a master regulator of adipocyte differentiation and metabolism. We review recent breakthroughs in the understanding of PPARγ gene regulation and function in the chromatin context. It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate with PPARγ to ensure adipocyte-specific genomic binding and function. We discuss how this differs in other PPARγ-expressing cells such as macrophages and how these genome-wide mechanisms are preserved across species despite modest conservation of specific binding sites. These emerging considerations inform our understanding of PPARγ function as well as of adipocyte development and physiology.
441 citations
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TL;DR: It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool, and a single set of cut points would be used for all components except waist circumference, for which further work is required.
Abstract: A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.
11,737 citations
TL;DR: This work has shown that abdominal obesity — the most prevalent manifestation of metabolic syndrome — is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis.
Abstract: Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.
4,002 citations
TL;DR: These findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot and Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
Abstract: Background— Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Methods and Results— Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, ...
2,501 citations
TL;DR: It is demonstrated that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where they fuse to form syncytia that sequester and scavenge the residual “free” adipocyte lipid droplet and ultimately form multinucleate giant cells, a hallmark of chronic inflammation.
2,235 citations
TL;DR: Although both IL-6 and TNF alpha are expressed by adipose tissue, the results show that there are important differences in their systemic release.
Abstract: We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.
2,169 citations