SIRT6 protects against metabolic damages and obesity of HFD by reducing hypothalamic inflammation

Sirt6 is a NAD+-dependent nuclear deacylase and a mono ADP-ribosylase. Neural-specific deletion of Sirt6 in mice leads to postnatal growth retardation due to somatotropic attenuation through low growth hormone (GH) and insulin-like growth factor 1 (IGF1) levels, and ultimately obesity. Recently, it was shown that mice overexpressing Sirt6 have a moderate youthful metabolic profile; they have improved glucose tolerance and are more active relative to WT littermates. Sirt6 transgenic mice fed a HFD are protected against WAT accumulation, elevated triglyceride and LDL cholesterol levels, and impaired glucose tolerance. Substantial evidence indicates that the brain, particularly the hypothalamus, is primarily responsible for the regulation of the altered energy homeostasis.

This study evaluated the effects of overexpression of SIRT6 on inflammation and energy metabolism parameters in the brain of old mice and mice subjected to high-fat diet-induced obesity.

Male C57BL mice were divided into control (purified low-fat diet) and obese (purified high-fat diet) groups. After 22 weeks, the animals were sacrificed and the brain was removed. SIRT6 overexpression had a beneficial effect on the hypothalamus of obese animals; it reversed the increase in inflammatory parameters and attenuated the insensitivity in glucose metabolism.

Furthermore, in the brains of Sirt6 transgenic mice fed HFD there was a decreased activity of inflammatory pathways in relation to WT littermates, which indicate an improved health condition. Since those processes are linked to obesity and weight gain in HFD, we present here Sirt6 as a target for treating this worldwide pandemic.