Adipokines: biological functions and metabolically healthy obese profile

Journal of Receptor, Ligand and Channel Research Dovepress open access to scientific and medical research Review Journal of Receptor, Ligand and Channel Research downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Open Access Full Text Article Adipokines: biological functions and metabolically healthy obese profile This article was published in the following Dove Press journal: Journal of Receptor, Ligand and Channel Research 15 May 2014 Number of times this article has been viewed Solange Silveira Pereira 1,2 Jacqueline I Alvarez-Leite 1,2 Laboratory for Atherosclerosis and Nutritional Biochemistry, Department of Biochemistry and Immunology, Institute of Biological Sciences, 2Alfa Institute of Gastroenterology, Clinics Hospital, Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil 1 Introduction Correspondence: Solange Silveira Pereira Laboratório de Aterosclerose e Bioquímica Nutricional, Bloco O4-Sl 110 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 6627 Avenida Antônio Carlos, Pampulha, Belo Horizonte, MG 31270-901, Brazil Email For a long time, adipose tissue was considered a deposit of energy. Nowadays, it is well known that the key role of adipose tissue in metabolism is as an endocrine organ responsible for the secretion of bioactive molecules termed “adipokines.”1 Adipokines have hormone function, act as growth factors that modulate insulin resistance, and act on the fat and glucose metabolism and participate in pro and anti-inflammatory responses.2,3 Deregulated adipokine expression caused by excessive adiposity and adipocyte dysfunction seen in obesity has been linked to the pathogenesis of several diseases through altered immune responses.1 Adipose tissue comprises mature adipocytes, preadipocytes, endothelial cells, fibroblasts, mast cells, and immune-system cells.4 Adipose tissue is not a uniform organ, and secretes different patterns of adipokines, depending on its location.5 Changes in specific adipokine profile lead to metabolic disturbances that play a central role in the 15 submit your manuscript | www.dovepress.com Journal of Receptor, Ligand and Channel Research 2014:7 15–25 Dovepress © 2014 Pereira and Alvarez-Leite. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/JRLCR.S36060 Powered by TCPDF (www.tcpdf.org) Abstract: Adipose tissue is an extremely active organ, and plays a fundamental role in the genesis of comorbidities associated with obesity. Since the discovery of leptin, an important focus has been assigned to adipose tissue as a key organ in the pathogenesis of metabolic disorders. The influence on the genesis of comorbidities associated with obesity is directly related to the pattern of adipokine secretion, the bioactive molecules produced on adipose tissue. The imbalance of adipokines consequent to the expansion of adipose tissue has been implicated in the development of the low-grade chronic inflammation seen in obesity. Adipokines act in a paracrine, autocrine, and endocrine fashion, influencing cytokine and chemokine secretions and hormonal and growth factors, as well as interfering with actions of insulin and lipid and glucose metabolism. The main adipokines include leptin, adiponectin, resistin, tumor-necrosis factor, interleukin 6, chemokine (C–C motif) ligand 2, interleukin 10, and transforming growth factor-β. The imbalance between pro- and anti-inflammatory adipokines on adipose tissue results in insulin resistance and the development of metabolic syndrome, type 2 diabetes, and cardiovascular disease. However, not all obese individuals develop these comorbidities or metabolic changes. Metabolically normal obese or metabolically healthy obese individuals have been the focus of research because of their absence of comorbidities. The profile of adipokines in adipose tissue of these individuals can be protective for the development of insulin resistance and metabolic disorders. This review emphasizes the roles of adipokines, the signaling pathways involved in the pathogenesis of inflammation and insulin resistance, and the profile found in metabolically healthy obese individuals. Keywords: adipokines, adipose tissue, obesity, metabolically healthy obese Journal of Receptor, Ligand and Channel Research downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Pereira and Alvarez-Leite development of insulin-resistant type 2 diabetes mellitus (T2DM) and cardiovascular diseases.6 Adipose tissue is dynamically involved in the regulation of cell function and the genesis of diseases via a complex network of signal endocrine, paracrine, and autocrine influencing the response of many tissues, including the hypothalamus, pancreas, liver, skeletal muscle, kidney, endothelium, and immune system, among others.5,7 These signals are mediated by adipokines and their mechanisms of action by binding to their receptors (Figure 1). Adipokines are classified as hormones, growth factors, angiogenic factors, and cytokines. Among them, leptin, adiponectin, resistin, monocytes, and macrophage chemotactic protein 1 (chemokine [C–C motif] ligand [CCL]-2), interleukin (IL)-6, IL-1β, tumor-necrosis factor (TNF), anti-inflammatory IL-10, and transforming growth factor (TGF)-β are the most studied8 (Table 1). The influence of adipose tissue in the development of metabolic disorders related to abdominal obesity has been well described.9 However, the presence of obesity-related metabolic disorders varies widely among obese individuals.10 A group of obese individuals with a favorable metabolic profile has been described.10–12 Individuals classified as metabolically normal obese or metabolically healthy obese (MHO) have normal cardiovascular risk, high insulin sensitivity, absence of dyslipidemia, and a favorable inflammatory profile.10,13 The mechanisms that may explain the favorable metabolic profile in these individuals are still unknown. Characteristics of adipose tissue, such as proinflammatory profile and expression of adipokines, may be involved.10 The interest in understanding the metabolically normal obese is increasing, due to the potential to elucidate the mechanisms of chronic diseases and translate them into treatment options. This review aims to describe the main biological functions of some adipok (...truncated)