Metformin inhibits inflammatory response and endoplasmic reticulum stress to improve hypothalamic aging in obese mice.

The hypothalamus, as a vital brain region for endocrine and metabolism regulation, undergoes functional disruption during obesity.The anti-aging effect of metformin has come into focus. However, whether it has the potential to ameliorate hypothalamic aging and dysfunction in the obese state remains unclear. In this study, obese mice were utilized to investigate the effects of metformin on the hypothalamus of obese mice. According to the results, metformin treatment resulted in improved insulin sensitivity, reduced blood glucose and lipid levels, as well as attenuation of hypothalamic aging, demonstrated by decreased SA-β-gal staining and downregulation of senescence markers. Additionally, metformin decreased the expression of endoplasmic reticulum stress-related proteins in neurons and reduced the inflammatory response triggered by microglia activation. Further mechanistic analysis revealed that metformin inhibited the expression and activation of STING and NLRP3 in microglia. These results reveal a possible mechanism by which metformin ameliorates hypothalamic aging.