Adipokines in inflammation and metabolic disease

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

ABSTRACT 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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    ABSTRACT: Catecholamines and adipokines function as hormones; catecholamines as neurotransmitters in the sympathetic nervous system, and adipokines as mediators of metabolic processes. It has become increasingly clear, however, that both also function as immunomodulators of innate and adaptive immune cells, including macrophages. Macrophages can respond to, as well as produce their own catecholamines. Dopamine, noradrenaline, and adrenaline are the most abundant catecholamines in the body, and can induce both pro-inflammatory and anti-inflammatory immune responses in macrophages, as well as non-immune processes such as thermogenesis. Though they are responsive to adipokines, particularly lipoproteins, leptin, and adiponectin, macrophages generally do not synthesize their own adipokines, with the exception being resistin-like molecules. Adipokines contribute to adverse metabolic and immune responses by stimulating lipid accumulation, foam cell formation and pro-inflammatory cytokine production in macrophages. Adipokines can also promote balance or resolution during metabolic and immune processes by promoting reverse lipid transport and expression of Th2 cytokines. This review will explore the mechanisms by which catecholamines and adipokines influence macrophage function in neural pathways, immunity and metabolism. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cytokine 02/2015; DOI:10.1016/j.cyto.2015.01.008 · 2.87 Impact Factor
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    ABSTRACT: We aimed to systematically review available literature linking adipokines to gestational diabetes mellitus (GDM) for a comprehensive understanding of the roles of adipokines in the development of GDM. We searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines and GDM through October 21, 2014. We included articles if they had a prospective study design (i.e., blood samples for adipokines measurement were collected before GDM diagnosis). Random-effects models were used to pool the weighted mean differences comparing levels of adipokines between GDM cases and non-GDM controls. Of 1523 potentially relevant articles, we included 25 prospective studies relating adipokines to incident GDM. Our meta-analysis of nine prospective studies on adiponectin and eight prospective studies on leptin indicated that adiponectin levels in the first or early second trimester of pregnancy were 2.25 μg/ml lower (95% CI: 1.75-2.75), whereas leptin levels were 7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than women who did not. Prospective data were sparse and findings were inconsistent for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vaspin. We did not identify prospective studies for several novel adipokines, including chemerin, apelin, omentin, or adipocyte fatty acid-binding protein. Moreover, no published prospective studies with longitudinal assessment of adipokines and incident GDM were identified. Adiponectin levels in the first or second trimester of pregnancy are lower among pregnant women who later develop GDM than non-GDM women, whereas leptin levels are higher. Well-designed prospective studies with longitudinal assessment of adipokines during pregnancy are needed to understand the trajectories and dynamic associations of adipokines with GDM risk. Published by Elsevier Inc.
    Metabolism: clinical and experimental 01/2015; 64(6). DOI:10.1016/j.metabol.2015.01.013 · 3.61 Impact Factor
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    ABSTRACT: Obesity is characterized by increased adipose tissue mass resulting from a chronic imbalance between energy intake and expenditure. Furthermore, there is a clearly defined relationship among fat mass expansion, chronic low-grade systemic inflammation and reactive oxygen species (ROS) generation; leading to ROS-related pathological events. In the past years, genome-wide association studies have generated convincing evidence associating genetic variation at multiple regions of the genome with traits that reflect obesity. Therefore, the present study aimed to evaluate the relationships among the gene polymorphisms ghrelin (GHRL–rs26802), ghrelin receptor (GHSR–rs572169), leptin (LEP–rs7799039), leptin receptor (LEPR–rs1137101) and fat mass and obesity-associated (FTO–rs9939609) and obesity. The relationships among these gene variants and the amount of DNA damage were also investigated. Three hundred Caucasian morbidly obese and 300 eutrophic (controls) women were recruited. In summary, the results demonstrated that the frequencies of the GHRL, GHSR, LEP and LEPR polymorphisms were not different between Brazilian white morbidly obese and eutrophic women. Exceptions were the AA-FTO genotype and allele A, which were significantly more frequent in obese women than in the controls (0.23% vs. 0.10%; 0.46 vs. 0.36, respectively), and the TT-FTO genotype and the T allele, which were less frequent in morbidly obese women (p < 0.01). Furthermore, significant differences in the amount of genetic lesions associated with FTO variants were observed only in obese women. In conclusion, this study demonstrated that the analyzed SNPs were not closely associated with morbid obesity, suggesting they are not the major contributors to obesity. Therefore, our data indicated that these gene variants are not good biomarkers for predicting risk susceptibility for obesity, whereas ROS generated by the inflammatory status might be one of the causes of DNA damage in obese women, favoring genetically related diseases as obesity comorbidities.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 01/2015; DOI:10.1016/j.mrfmmm.2015.01.004 · 4.44 Impact Factor


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