Sex-Specific Differences in Gestational Diabetes Mellitus-Induced Cardiac Hypertrophy and Altered Mitochondrial Protein Acetylation in the Offspring Heart and the Protective Role of SIRT3

Gestational diabetes mellitus (GDM) increases risk of cardiovascular disease in offspring later in life, yet mechanisms, particularly sex-specific differences, remain unclear. GDM induces abhorrent protein acetylation in offspring cardiac mitochondria, partially due to reduced expression of deacetylase proteins, such as Sirtuin-3 (SIRT3). Protein acetylation is a major regulatory mechanism of metabolic enzymes in cardiac mitochondria. We hypothesize that increasing cardiac SIRT3 in offspring protects from GDM-induced cardiac dysfunction.