Catestatin (Chromogranin A352–372) and Novel Effects on Mobilization of Fat from Adipose Tissue through Regulation of Adrenergic and Leptin Signaling

Abstract

Background: Mice lacking the neurosecretory protein Chromogranin A are obese, presumably because of resistance to catecholamines and leptin. Results: Catestatin (CST) reduces adiposity, an effect likely mediated by restoring leptin sensitivity and modulating adrenergic signaling. Conclusion: CST promotes lipolysis by blocking ␣-AR signaling and stimulating fatty acid oxidation. Significance: We propose CST as a candidate antiobesity agent.

Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo

“…The extracellular function of CgA includes the generation of bioactive peptides, such as the insulin-regulatory hormone pancreastatin (Bandyopadhyay et al 2015; Gayen et al 2009b; Sanchez-Margalet et al 2010; Tatemoto et al 1986), the vasodilating and cardioprotective vasostatin (Aardal et al 1993; Tota et al 2008), the anti-adrenergic (Mahata et al 2003; Mahata, et al 2010; Mahata et al 1997), anti-hypertensive (Mahapatra et al 2005), anti-obesity (Bandyopadhyay et al 2012), proangiogenic (Theurl et al 2010) and cardioprotective catestatin (Angelone et al 2008; Mahata et al 2010) and the pro-adrenergic serpinin (Tota et al 2012). The intracellular function of CgA includes the initiation and regulation of DCV biogenesis and sequestration of hormones in neuroendocrine cells (Elias et al 2012; Iacangelo and Eiden 1995; Kim et al 2001; Taupenot et al 2002).…”

Functional Genetic Variants of the Catecholamine-Release-Inhibitory Peptide Catestatin in an Indian Population

“…43) that is in strong linkage disequilibrium with the CST G364S SNP. Likewise, CST has recently been reported to increase lipolysis (triglyceride hydrolysis) and lipid mobilization in adipose tissues via its interaction with ␣2-adrenergic receptor and leptin receptor (19). The higher triglyceride levels in subjects carrying the Ser-364 allele could be because of diminished lipolytic activity of this CST variant, perhaps due to lower antagonistic activity of the CST-Ser-364 peptide on ␣2-adrenergic receptor or lower activity on the leptin receptor similar to its nAChR-mediated catecholamine-release-inhibitory function.…”

“…Consistently, mice lacking CST (generated by systemic deletion of its precursor CHGA molecule) displayed severe hypertension that could be rescued by administration of human CST peptide (7). Very recently, CST has been reported to act as an insulin-sensitizing agent (perhaps via inhibition of gluconeogenesis) as well as to regulate lipogenesis, lipolysis, and fatty acid oxidation (4,19). Thus, CST is emerging as a novel regulator of cardiovascular/metabolic functions.…”

A common genetic variant of the chromogranin A-derived peptide catestatin is associated with atherogenesis and hypertension in a Japanese population

“…The exon-7 region of CHGA was PCR amplified using Tks Gflex DNA Polymerase tion-inhibitory effect via blockade of neuronal nicotinic acetylcholine receptor (nAChR) [5][6][7][8][9]. In addition, CST has been reported to act as a novel regulator of glucose/insulin homeostasis (via inhibition of gluconeogenesis) as well as lipogenesis, lipolysis, and fatty acid oxidation [10,11].…”