Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice

BackgroundChronic inflammation and metabolic dysregulation may eventually cause tissue damage in obesity-related diseases such as type 2 diabetes. The effects of SIRT1 on integration of metabolism and inflammation may provide a therapeutic target for treatment of obesity-related diseases. We examined the underlying mechanism of moderate intensity aerobic exercise on kidney and liver in obese diabetic db/db mice, mainly focusing on inflammation and metabolic dysfunction.MethodsFunctional and morphological alterations and metabolic and inflammatory signaling were examined in type 2 diabetic db/db mice with or without exercise training (5.2m/min, 1h/day, and 5days/week for a total of 8weeks).ResultsExercise training prevented weight gain in db/db+Ex mice, but it did not reduce glucose and insulin levels. Exercise lowered serum creatinine, urea, and triglyceride levels and hepatic AST and ALT activity in db/db+Ex mice. Reduced kidney size and morphological alterations including decreased glomerular cross-sectional area and hepatic macrovesicles were observed in db/db+Ex mice compared with untrained db/db mice. Mechanistically, preventing loss of SIRT1 through exercise was linked to reduced acetylation of NF-B in kidney and liver of db/db+Ex mice. Exercise increased citrate synthase and mitochondrial complex I activity, subunits of mitochondrial complexes (I, II, and V) and PGC1 at protein level in kidney of db/db+Ex mice compared with non-exercise db/db mice. Changes in enzyme activity and subunits of mitochondrial complexes were not observed in liver among three groups.ConclusionExercise-induced upregulation of SIRT1 attenuates inflammation and metabolic dysfunction, thereby alleviating the progression of diabetic nephropathy and hepatic steatosis in type 2 diabetes mellitus.