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

Leilei Yang; Peng Lu; Xiangyu Qi; Qian Yang; Luna Liu; Tao Dou; Qingbo Guan; Chunxiao Yu

doi:10.1016/j.isci.2023.108082

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

iScience. 2023 Sep 27;26(10):108082. doi: 10.1016/j.isci.2023.108082. eCollection 2023 Oct 20.

Authors

Leilei Yang^{1

2

3

4}, Peng Lu^{1

2

3

4}, Xiangyu Qi^{1

2

3

4}, Qian Yang^{1

2

3

4}, Luna Liu^{1

2

3

4}, Tao Dou^{1

2

3

4}, Qingbo Guan^{1

2

3

4}, Chunxiao Yu^{1

2

3

4}

Affiliations

¹ Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
² Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, China.
³ Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.
⁴ Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China.

Abstract

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.

Keywords: Immunology; Molecular biology; Neuroscience; Physiology.