Myocardin reverses insulin resistance and ameliorates cardiomyopathy by increasing IRS-1 expression in a murine model of lipodystrophy caused by adipose deficiency of vacuolar H⁺-ATPase V0d1 subunit.

ABSTRACT: Aim: Adipose tissue (AT) dysfunction that occurs in both obesity and lipodystrophy is associated with the development of cardiomyopathy. However, it is unclear how dysfunctional AT induces cardiomyopathy due to limited animal models available. We have identified vacuolar H⁺-ATPase subunit V_od1, encoded by Atp6v0d1, as a master regulator of adipogenesis, and adipose-specific deletion of Atp6v0d1 (Atp6v0d1^AKO) in mice caused generalized lipodystrophy and spontaneous cardiomyopathy. Using this unique animal model, we explore the mechanism(s) underlying lipodystrophy-related cardiomyopathy. Methods and Results: Atp6v0d1^AKO mice developed cardiac hypertrophy at 12 weeks, and progressed to heart failure at 28 w

SUBMITTER: Yuan W 

PROVIDER: S-EPMC10945344 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature