The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy.

ABSTRACT: Sirtuins (Sirts) are implicated in regulating a myriad of biologic functions ranging from cell growth and metabolism to longevity. Here, we show that nuclear Sirt, Sirt6, and mitochondrial Sirt, Sirt3, regulate each other's activity and protect the heart from developing diabetic cardiomyopathy. We found that expression of both Sirt6 and Sirt3 was reduced in cardiomyocytes treated with palmitate and in hearts of mice fed with a high-fat, high-sucrose (HF-HS) diet to develop obesity and diabetes. Conversely, whole-body overexpressing Sirt6 transgenic (Tg.Sirt6) mice were protected from developing obesity and insulin resistance when fed with the same HF-HS diet. The hearts of Tg.Sirt6 mice were also protected from mitochondrial fragmentation and decline of Sirt3, resulting otherwise from HF-H

SUBMITTER: Kanwal A 

PROVIDER: S-EPMC6766651 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature