Targeting ATGL to rescue BSCL2 lipodystrophy and its associated cardiomyopathy.

ABSTRACT: Mutations in BSCL2 gene underlie human type 2 Berardinelli-Seip Congenital Lipodystrophy (BSCL2) disease. Global Bscl2-/- mice recapitulate human BSCL2 lipodystrophy and develop insulin resistance and hypertrophic cardiomyopathy. The pathological mechanisms underlying the development of lipodystrophy and cardiomyopathy in BSCL2 are controversial. Here we report that Bscl2-/- mice develop cardiac hypertrophy due to increased basal IGF1 receptor (IGF1R)-mediated PI3K/AKT signaling. Bscl2-/- hearts exhibited increased adipose triglyceride lipase (ATGL) protein stability and expression causing drastic reduction of glycerolipids. Excessive fatty acid oxidation was overt in Bscl2-/- hearts, partially attributing to the hyperacetylation of cardiac mitochondrial proteins. Intriguingly, pharmacolog

SUBMITTER: Zhou H 

PROVIDER: S-EPMC6675548 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature