Aerobic exercise improves metabolic disorders and multi-organ damage in diabetic rats by activating the Sirt1/Creb1/Ppargc1a axis

To investigate the effects of aerobic exercise and exhaustive anaerobic exercise on organ glucose metabolism and function in type 2 diabetic rats and the underlying mechanisms.

Forty male SD rats were randomly divided into normal control group (n=10) and diabetic model group (n=30). In the latter group, type 2 diabetes was induced by high-fat and high-sugar diet combined with streptozotocin injection. The diabetic rat models were further assigned to diabetic control, aerobic exercise and exhaustive anaerobic exercise groups (n=10) with an 8-week exercise intervention. General physiological indicators of the rats were measured, and liver, quadriceps, heart and prefrontal cortex tissues were collected for HE, Masson, PAS staining and immunohistochemistry. Hepatic expression of key metabolic enzymes and genes were detected using Western blotting and qPCR.

Compared with the normal control rats, the diabetic rats had significantly increased body weight, liver index, fasting blood glucose and serum levels of metabolic markers with severe hepatic steatosis, fibrosis, glycogen loss, skeletal and cardiac muscle damages, and downregulated DRD1/DRD5, 5-HT and TH in the prefrontal cortex. Aerobic exercise markedly reversed these abnormalities, alleviated organ pathological lesions, suppressed hepatic G6PC and glycolytic enzymes, upregulated Sirt1 mRNA, and restored cortical neurotransmitter-related proteins in the diabetic rats. Exhaustive anaerobic exercise lowered body weight and fasting glucose of the diabetic rats, but caused significant increase of serum metabolic indicators, worsened hepatic steatosis and tissue fibrosis, reduced glycogen, and further reduction of neurotransmitter expressions in the brain.

Aerobic exercise protects organ function of diabetic rats by regulating glucose-lipid metabolism, relieving inflammation and fibrosis and improving neurotransmitter function, while exhaustive anaerobic exercise can aggravate metabolic disorders and cause tissue damage.