Conversely, whole-body overexpressing Sirt6 transgenic (Tg.Sirt6) mice were protected from developing obesity and insulin resistance when fed with the same HF-HS diet.
Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues.
These roles that were determined by genetic studies include promoting pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride synthesis, and suppressing adiposity, suggesting that SIRT6 activators are promising molecules for treating obesity and diabetes.
Mice overexpressing the longevity protein SIRT6 or deficient for the liver's most prevalent microRNA miR-122 display a similar set of phenotypes, including improved lipid profile and protection against damage linked to obesity.
SIRT6 has been demonstrated to exert protective effects on endothelial cells and is closely associated with lipid metabolism, glucose metabolism, and obesity, indicating an important role in the pathogenesis and progression of coronary artery disease (CAD).