Annual Research & Review in Biology 17(1): 1-11, 2017; Article no.ARRB.36281 ISSN: 2347-565X, NLM ID: 101632869 Adiponectin: Obesity and Development of Different Diseases Q. F. B. Amado Israel de la Cruz Galindo1, Jonnathan Guadalupe Santillán Benítez1* and Enrique Morales Avila1 1Faculty of Chemistry, Autonomus University of the State of México, Paseo Colón S/N, Residencial Colón, 50120, Toluca de Lerdo, México. Authors’ contributions This work was carried out in collaboration between all authors. Author QFBAICG designed the study, performed the statistical analysis, wrote the protocol, and wrote the first draft of the manuscript. Authors JGSB and EMA managed the analyses of the study through the PRODEP project DSA / 103.5 / 16/10569. Author JGSB managed the literature searches. All authors read and approved the final manuscript. Article Information DOI: 10.9734/ARRB/2017/36281 Editor(s): (1) George Perry, Dean and Professor of Biology, University of Texas at San Antonio, USA. Reviewers: (1) Mohamed M. Abdel-Daim, Suez Canal University, Egypt. (2) Mra Aye, Melaka Manipal Medical College, Melaka, Malaysia. Complete Peer review History: http://www.sciencedomain.org/review-history/20952 Received 21st August 2017 th Review Article Accepted 6 September 2017 Published 13th September 2017 ABSTRACT Adiponectin is an adipokine abundantly expressed in adipose tissue, which has been well characterized, demonstrating its beneficial effect on human health, circulates in the bloodstream in various isoforms, playing different roles in the balance of energy homeostasis. Adiponectin is an insulin sensitizing hormone that exerts its action through AdipoR1, AdipoR2 and T-cadherin receptors. AdipoR1 is abundantly expressed in muscle, whereas AdipoR2 is expressed predominantly in the liver. Adiponectin is inversely proportional to obesity, diabetes and other states of insulin resistance; this review presents current findings regarding regulation, production and biological effects. Adiponectin acts by activating AMPk (AMP-activated protein kinase) and thus the enzymatic modulation so that the signaling pathways play an important role in the regulation, in addition to the above it has been demonstrated that the deregulation in the biogenesis and function of the miRNAs contributes to the appearance and development of diverse diseases. _____________________________________________________________________________________________________ *Corresponding author: E-mail: [email protected]; Galindo et al.; ARRB, 17(1): 1-11, 2017; Article no.ARRB.36281 Keywords: Adiponectin; adipokine; obesity; AdipoR1; AdipoR2. ABBREVIATIONS HER2 : Human epidermal growth factor receptor 2. HER3 : Human epidermal growth factor receptor 3. RTKN : Rhotekin coding gene. ESR1 : Estrogen receptor coding gene 1. ER : Estrogen receptor. H-RAS : Gene encoding HRAS proteins. HMGA2 : High-mobility group AT-hook 2. LIN28 : Encodes a LIN-28 family RNA-binding protein. PEBP1 : Encodes a member of the phosphatidylethanolamine-binding family of proteins and has been shown to modulate multiple signaling pathways. ERBB3 : Receptor tyrosine-protein kinase, also known as HER3. CDC25C : encodes a conserved protein that plays a key role in the regulation of cell division. EVI-1 : Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes. BCL-2 : Protein family that regulates apoptosis. TIPM1 : Metallopeptidase inhibitor 1. PDCD4 : Programmed cell death 4. PTEN : phosphatase and tensin homolog. MASPIN : mammary serine protease inhibitor. RHOA : Family of genes homologous to Ras, member A. FOXO2 : Forkhead Box Protein O2. E-CADHERIN : Calcium-dependent cell adhesion proteins. FOXO3a : Forkhead Box Protein 3A. ERα : Estrogen receptor alpha. HOXD10 : homeobox D10. NF-Kappa B : Nuclear factor kappa-light-chain-enhancer of activated B cells. 1. INTRODUCTION process of these diseases is adipose tissue, which is an endocrine organ that produces Obesity is a multifactorial disease produced by biologically active molecules defined as the interaction of genetic and environmental "adipokines", involved in the homeostasis of factors, caused by lifestyle, characterized by an various physiological processes [6,7]. Therefore, excessive increase of body fat, produced by an alterations in adipose tissue, causes changes in imbalance between ingestion and energy the serum concentrations of adipokines, [6] and expenditure [1,2]. Obesity has become a public against this background, much of the scientific health problem worldwide and its prevalence has research is directed towards the understanding increased dramatically in developed and of the pathological mechanisms of obesity, developing countries [2,3]. In this sense, Mexico allowing to establish clear associations between ranks second in the world prevalence of obesity, biochemical and anthropometric indicators with where over 70% of the adult population is the risk of complications derived from obesity. overweight and obese, and resulting in economic However, an emerging field is the strong and public health repercussions [4]. relationship between adipokine serum concentrations, particularly adiponectin, with Epidemiological studies have shown that due to obesity and its involvement in pathophysiological the physiological condition that occurs in obesity, processes [8]. it is a risk factor for the development of different diseases, such as cardiovascular, diabetes 2. OVERVIEW OF ADIPONECTIN mellitus, hypertension and different types of cancer, including breast cancer [1,5]. In this Adiponectin, one of many hormones secreted by sense, accumulation of fat causes a deregulation adipose tissue, was characterized in the 1990s in the production of adipokines which contributes and has received various names according to the strongly to the onset of obesity related to the description of various research groups [9]. development of various diseases, the Plasma concentrations of adiponectin in the indisputable protagonist in the pathophysiological human are ~ 5-30 μg / ml, this is one of the most 2 Galindo et al.; ARRB, 17(1): 1-11, 2017; Article no.ARRB.36281 abundant proteins in circulation (0.01% of total light-chain-enhancer of activated B cells). AMPK proteins) [10]. The biological effects of is activated by the adapter protein APPL-1 adiponectin not only depend on blood (adaptor protein, phosphotyrosine interaction, PH concentrations, but also important the expression domain and leucine zipper containing 1) and of different isoforms of receptors in different kinase β1 (LKB1), the activity of LKB1 (liver tissues [11]. kinase B1) depends on the interaction with two proteins STE 20 (STRAD) and MO25, this Adiponectin plays critical roles in metabolism, complex phosphorylates AMPK and regulates regulation and maintenance for energy several pathways, such as apoptosis, throughout the body, the main target organs are proliferation, angiogenesis and energy liver and skeletal muscle, however, during the metabolism. AMPK phosphorylates the TSC2 last few decades numerous studies have shown (Tuberous Sclerosis Complex 2) protein, which that adiponectin exerts several effects on other negatively regulates protein synthesis and cell organs in different contexts [12] (Fig. 1). proliferation. Adiponectin also affects PI3K / AKT signaling, which is involved in cell growth and Adiponectin is a 30 kDa protein, composed of proliferation, AKT phosphorylates TSC2 which in 244 amino acids and encodes the long arm of turn stimulates mTOR signaling by neutralizing chromosome 3 (locus 3q27). The adiponectin the effects of activated AMPK. In treatment with gene consists of 3 exons and 2 introns, adiponectin in breast cancer cells the structurally containing 4 domains [15,16], it is phosphorylation of PI3k and AKT induces the synthesized as a single subunit and by activation of AMPK and suppresses the mTOR processes of hydroxylation and glycosylation, pathway thereby inhibiting cell growth. Low various isoforms circulating in the plasma as doses of adiponectin inhibit ERK1 (extracellular trimer (low molecular weight LMW), hexamers signal–regulated kinases) / 2 signaling and (MMW average molecular weight) or multimers reduce viability in breast cancer cells, and (high molecular weight HMW) are originated. The adiponectin induces cell cycle arrest through monomer form lacks biological activity, whereas down-regulation of C-myc, cyclin D, and Bcl HMW is the main active form, and is strongly levels. Increases the expression of P53 (cellular associated with insulin resistance, metabolic tumor antigen), P21 (cyclin-dependent kinase syndrome and cardiovascular disease inhibitor 1) and Bax [22,23,24,25,26]. [15,16,17,19]. The action of adiponectin is mediated by 3 types 2.2 Adiponectin Regulation of receptors: AdipoR1, AdipoR2 and T- Cadherin. The first two consist of 7 transmembrane White adipose tissue, under normal physiological domains, with the internal N-terminal region and conditions, controls the use of substrates in other the outer C-terminal region, structurally and tissues by releasing hormones such as functionally different from the G- protein coupled adiponectin that is transported through the receptor family [15,20]. AdipoR1 is abundantly bloodstream to other organs, where through expressed in skeletal muscle and endothelial signaling pathways mediated by their receptors, cells, AdipoR2 is expressed predominantly in the they activate key enzymes of lipid and glucose liver. The third is T-cadherin, lacking a metabolism [27]. Both adiponectin receptors