| First Author | Bandyopadhyay GK | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 27 | Pages | 23141-51 |
| PubMed ID | 22535963 | Mgi Jnum | J:188389 |
| Mgi Id | MGI:5440400 | Doi | 10.1074/jbc.M111.335877 |
| Citation | Bandyopadhyay GK, et al. (2012) Catestatin (chromogranin A(352-372)) and novel effects on mobilization of fat from adipose tissue through regulation of adrenergic and leptin signaling. J Biol Chem 287(27):23141-51 |
| abstractText | Chromogranin A knock-out (Chga-KO) mice display increased adiposity despite high levels of circulating catecholamines and leptin. Consistent with diet-induced obese mice, desensitization of leptin receptors caused by hyperleptinemia is believed to contribute to the obese phenotype of these KO mice. In contrast, obesity in ob/ob mice is caused by leptin deficiency. To characterize the metabolic phenotype, Chga-KO mice were treated with the CHGA-derived peptide catestatin (CST) that is deficient in these mice. CST treatment reduced fat depot size and increased lipolysis and fatty acid oxidation. In liver, CST enhanced oxidation of fatty acids as well as their assimilation into lipids, effects that are attributable to the up-regulation of genes promoting fatty acid oxidation (Cpt1alpha, Pparalpha, Acox, and Ucp2) and incorporation into lipids (Gpat and CD36). CST did not affect basal or isoproterenol-stimulated cAMP production in adipocytes but inhibited phospholipase C activation by the alpha-adrenergic receptor (AR) agonist phenylephrine, suggesting inhibition of alpha-AR signaling by CST. Indeed, CST mimicked the lipolytic effect of the alpha-AR blocker phentolamine on adipocytes. Moreover, CST reversed the hyperleptinemia of Chga-KO mice and improved leptin signaling as determined by phosphorylation of AMPK and Stat3. CST also improved peripheral leptin sensitivity in diet-induced obese mice. In ob/ob mice, CST enhanced leptin-induced signaling in adipose tissue. In conclusion, our results implicate CST in a novel pathway that promotes lipolysis and fatty acid oxidation by blocking alpha-AR signaling as well as by enhancing leptin receptor signaling. |
