Adipokines in inflammation and metabolic disease. Nat Rev Immunol

Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya, 466-8550 Japan.
Nature Reviews Immunology (Impact Factor: 34.99). 02/2011; 11(2):85-97. DOI: 10.1038/nri2921
Source: PubMed


The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

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    • "Given the measured white adipose tissue mass differences (Figure 1D), the data are consistent with an approximate doubling of adipocyte number in the obese-Trim28 +/D9 animals. Plasma levels of the pro-inflammatory adipokines TNF-a and resistin, of C-reactive protein (Ouchi et al., 2011), and of the plasma-soluble receptor RAGE (Alexiou et al., 2010) were unremarkable (Figure S1H). Further, no evidence was found of secondary metabolic complications such as hepatosteatosis (Figure S1I), though our own previous work examining older cohorts has shown this as a potential endpoint (Whitelaw et al., 2010). "
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    ABSTRACT: More than one-half billion people are obese, and despite progress in genetic research, much of the heritability of obesity remains enigmatic. Here, we identify a Trim28-dependent network capable of triggering obesity in a non-Mendelian, "on/off" manner. Trim28(+/D9) mutant mice exhibit a bi-modal body-weight distribution, with isogenic animals randomly emerging as either normal or obese and few intermediates. We find that the obese-"on" state is characterized by reduced expression of an imprinted gene network including Nnat, Peg3, Cdkn1c, and Plagl1 and that independent targeting of these alleles recapitulates the stochastic bi-stable disease phenotype. Adipose tissue transcriptome analyses in children indicate that humans too cluster into distinct sub-populations, stratifying according to Trim28 expression, transcriptome organization, and obesity-associated imprinted gene dysregulation. These data provide evidence of discrete polyphenism in mouse and man and thus carry important implications for complex trait genetics, evolution, and medicine. VIDEO ABSTRACT.
    Full-text · Article · Jan 2016 · Cell
    • "Beyond its energy storage capacity, WAT is an endocrine organ secreting multiple bioactive molecules known as adipokines, among which are the monochemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-), LPSbinding protein (LBP), leptin, and adiponectin [3] [4]. Dysregulated production or secretion of these adipokines, caused by WAT dysfunction and excess adiposity, contribute to the development of the obesity-associated low-grade inflammation [4] [5]. Dietary fat absorption in the body is primarily governed by the small intestine whose lipid absorption capacity adapts to ingested fat amount. "
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    ABSTRACT: Scope: Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects using a new polar lipid emulsifier from milk (MPL) instead of soybean lecithin (SPL) on adipose tissue and intestinal mucosa function. Methods and results: Four groups of C57BL6 mice received for 8 weeks a low-fat diet (LF) or a high-fat diet devoid of polar lipids (HF) or a high-fat diet including MPL (HF-MPL) or SPL (HF-SPL). Compared with HF diet, HF-SPL diet increased white adipose tissue (WAT) mass (P<0.05), with larger adipocytes (P<0.05) and increased expression of MCP-1, LBP and leptin (P<0.05). This was not observed with HF-MPL diet despite similar dietary intakes and increased expression of FATP4 and MTTP, involved in lipid absorption, in upper intestine (P<0.05). HFP-MPL mice had a lower expression in WAT of CD68, marker of macrophage infiltration, vs HF and HFP-SPL mice (P<0.05), and more goblet cells in the colon (P<0.05). Conclusions: Unlike SPL, MPL in a high fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Molecular Nutrition & Food Research
    • "As such, it functions as an endocrine organ that regulates metabolic processes in the body through the excretion of hormones[5]. Many of these adipocyte-derived hormones, generally referred to as adipokines, also have immuno-modulatory roles[6], which we will describe in more detail below. The origin of adipose organs has been studied most extensively in mice. "
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    ABSTRACT: Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions.
    No preview · Article · Nov 2015 · Seminars in Immunology
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