Sirtuin 6 supra-physiological overexpression in hypothalamic pro-opiomelanocortin neurons promotes obesity via the hypothalamus-adipose axis.

Abstract

Sirtuin 6 (Sirt6), a member of the Sirtuin family, has important roles in maintaining glucose and lipid metabolism. Our previous studies demonstrated that the deletion of Sirt6 in pro-opiomelanocortin (POMC)-expressing cells by the loxP-Cre system resulted in severe obesity and hepatic steatosis. However, whether overexpression of Sirt6 in hypothalamic POMC neurons could ameliorate diet-induced obesity is still unknown. Thus, we generated mice specifically overexpressing Sirt6 in hypothalamic POMC neurons (PSOE) by stereotaxic injection of Cre-dependent adeno-associated viruses into the arcuate nucleus of Pomc-Cre mice. PSOE mice showed increased adiposity and decreased energy expenditure. Furthermore, thermogenesis of BAT and lipolysis of WAT were both impaired, caused by reduced sympathetic nerve innervation and activity in adipose tissues. Mechanistically, Sirt6 overexpression decreasing STAT3 acetylation, thus lowering POMC expression in the hypothalamus underlined the observed phenotypes in PSOE mice. These results demonstrate that Sirt6 overexpression specifically in the hypothalamic POMC neurons exacerbates diet-induced obesity and metabolic disorders via the hypothalamus-adipose axis.

• Authors: Qin Tang, Qinhui Liu, Xuping Yang, Tong Wu, Cuiyuan Huang, Jinhang Zhang, Zijing Zhang, Guorong Zhang, Yingnan Zhao, Jian Zhou, Hui Huang, Yan Xia, Jiamin Yan, Yanping Li, Jinhan He
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 35 Issue 3 Pg. e21408 (03 2021) ISSN: 1530-6860 [Electronic] United States
• PMID: 33583107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Federation of American Societies for Experimental Biology.

Chemical References

• Leptin
• Pro-Opiomelanocortin
• Sirt6 protein, mouse
• Sirtuins

Topics

• Adipose Tissue (metabolism)
• Animals
• Arcuate Nucleus of Hypothalamus (metabolism)
• Energy Metabolism (physiology)
• Hypothalamus (metabolism)
• Leptin (metabolism)
• Mice, Inbred C57BL
• Neurons (metabolism)
• Obesity (etiology, metabolism)
• Pro-Opiomelanocortin (genetics, metabolism)
• Sirtuins (metabolism)
• Mice