Adiponectin is an adipokine whose circulating level is

Adiponectin is an adipokine whose circulating level is depleted in a number of metabolic diseases including insulin resistance, diabetes and cancer (Khan et al., 2015, Singh et al., 2014a, Singh et al., 2014b, Yamauchi et al., 2014). Despite its importance in health and pathophysiology, adiponectin replenishment therapy is not possible owing to the large size of this peptide and its complex multimerization properties (Singh et al., 2014a, Singh et al., 2014b, Yamauchi et al., 2014). Recently, we identified a small molecule orally active adiponectin receptor (AdipoR) agonist called GTDF that shows a binding preference for AdipoR1 (Singh et al., 2014a, Singh et al., 2014b). Our results in osteoblasts revealed that MuRF1 and atrogin-1 were also expressed in bone Org 25543 and their expressions were increased during early-onset diabetes-induced osteopenia (Khan et al., 2015). In the same study GTDF was found to downregulate MuRF1 and atrogin-1 and enhance the expression and activity of PGC-1α via AdipoR1 (Khan et al., 2015). Adiponectin, in particular globular adiponectin that has a strong affinity for AdipoR1 also has been shown to induce myogenic differentiation (Fiaschi et al., 2009). In this study we thus investigated if GTDF also could induce myogenesis and if activation of adiponectin signaling events by GTDF or gAd could protect from skeletal muscle atrophy.
Material and methods
Results and discussion
Authorship contribution
Acknowledgements SS and NC acknowledge funding from CSIR network project ASTHI, AKT acknowledges funding from CSIR network project INDEPTH. RR acknowledges CSIR network project SPLENDID. AKS & AG were supported by fellowships from CSIR. SS, SC, SK & HK were supported by fellowships from UGC. SaK was supported by Nehru postdoctoral fellowship fromCSIR. Authors thank Dr. Annette G Beck-Sickinger (Institute of Biochemistry, Leipzig University, Germany) for the kind gift of pET-globular adiponectin plasmid (gAd_pET15b). Authors also thank Md. Parvez Khan (Division of Endocrinology, CSIR-CDRI) for help with myotube quantification.
Introduction Adipose tissue is an organ that stores lipids and secretes a variety of hormones that influence physiological functions of other organs related to growth, immunity, and reproduction. Following the discovery of leptin nearly two decades ago (Frederich et al., 1995, Halaas et al., 1995), secretion and biological functions of several adipose tissue hormones such as adiponectin, resistin and chemerin, and several cytokines have been characterized in humans and rodent models (Beutler et al., 1985, Goralski et al., 2007, Kern et al., 2001, Steppan et al., 2001). Despite the recent developments in sequencing of the chicken genome, adipose hormones remain enigmatic as many classical adipose hormones such as leptin and resistin have not been identified in the chicken genome (Friedman-Einat et al., 1999, Sharp et al., 2008). Avian adipose tissue is an interesting organ as it undergoes constant remodeling to meet the metabolic demands of growth, reproduction, and migration. In addition, avian adipose tissue is constantly exposed to a glucose level exceeding 17.5mM that is considered hyperglycemic to mammalian adipocytes. A thorough knowledge of adipose tissue is therefore critical for understanding the uniqueness of metabolic conditions encountered in avian species. This mini-review summarizes our understanding of the unique biochemical properties and functions of the most abundant adipose tissue hormone, adiponectin, and its receptors, AdipoR1 and AdipoR2.
Adiponectin in mammalian and avian Species Adiponectin (also called Acrp30, apM1, GBP28, or adipoQ) is a 30kDa adipocytokine hormone exclusively secreted from the adipose tissue in mammals (Hu et al., 1996, Maeda et al., 1996, Nakano et al., 1996, Scherer et al., 1995). The adiponectin gene is highly conserved among several mammalian species and codes for a 244-amino acid protein that belongs to a family of C1q globular domain proteins (Kishore and Reid, 1999, Kishore and Reid, 2000). Adiponectin is the most abundant protein in human adipose tissue, and also the most abundant hormone in human plasma (1.9–17μg/ml), accounting for 0.01% of plasma proteins (Arita et al., 1999). Adiponectin circulates as a trimer, hexamer, heavy molecular weight forms, and also as small proteolytic cleavage products in mouse and human plasma (Fruebis et al., 2001, Kishida et al., 2003). Adiponectin has multiple beneficial effects on glucose utilization and insulin sensitivity thereby aiding in the prevention of type 2 diabetes and cardiovascular diseases in humans (reviewed in Whitehead et al. (2006)). Decreased plasma adiponectin levels are associated with the development of insulin resistance, type 2 diabetes, and cardiovascular diseases in humans and rodent models. Although secreted from adipose tissue, adiponectin levels in the circulation were found to be lower, paradoxically, in obese human subjects (Arita et al., 1999). Despite its potential importance in avian species, adiponectin has not been thoroughly investigated. Therefore, we began our investigations by characterizing the biochemistry and expression of chicken adiponectin, as described below.