Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents

Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4^+/- mice (hyperglycemic and hyperinsulinemic mice).

Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4^+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions.

In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.