“…Despite the fact that mice lacking Sirt3 are phenotypically normal under basal conditions [57], Sirt3 deficient mice placed on a high fat diet (HFD) display accelerated development of metabolic syndrome including: accelerated insulin resistance, obesity, hyperlipidemia and steatohepatitis [58]. In mouse muscle, Sirt3 is necessary to preserve glucose oxidation and mitochondrial function thereby opposing the metabolic switch observed during HFD-induced insulin resistance [37,59,60]. In addition, Sirt3 has been directly linked to cardiomyocyte homeostasis by the observation that aged Sirt3-KO mice develop cardiac hypertrophy, a pathological condition caused by enlargement of the heart muscle that can lead to heart failure [41,61,62].…”