Sirtuin 3: a major control point for obesity-related metabolic diseases?

• Reversible lysine acetylation has emerged as a key regulator of mitochondrial fatty acid oxidation and antioxidant defense.
• Sirtuin 3 is the primary mitochondrial deacetylase, but is downregulated in obesity, resulting in mitochondrial protein hyperacetylation.
• Animals lacking sirtuin 3 display accelerated weight gain and development of the metabolic syndrome on a high fat diet.
• Whether restoration of sirtuin 3 activity in obesity holds metabolic benefit remains unknown.

Obesity and obesity-related complications are epidemic issues currently plaguing much of the developed world with increasing associated morbidity, mortality, and economic burden. In this brief review, we discuss emerging evidence and remaining questions regarding the possible role for mitochondrial sirtuin 3 as a therapeutic target for the treatment of obesity-related metabolic diseases.