Yang Leilei, Lu Peng, Qi Xiangyu, Yang Qian, Liu Luna, Dou Tao, Guan Qingbo, Yu Chunxiao
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.
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, China.
iScience. 2023 Sep 27;26(10):108082. doi: 10.1016/j.isci.2023.108082. eCollection 2023 Oct 20.
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.
下丘脑作为内分泌和代谢调节的重要脑区，在肥胖过程中会发生功能紊乱。二甲双胍的抗衰老作用已受到关注。然而，其是否有潜力改善肥胖状态下的下丘脑衰老和功能障碍仍不清楚。在本研究中，利用肥胖小鼠来研究二甲双胍对肥胖小鼠下丘脑的影响。根据结果，二甲双胍治疗可改善胰岛素敏感性，降低血糖和血脂水平，并减轻下丘脑衰老，这通过SA-β-半乳糖苷酶染色减少和衰老标志物下调得以证明。此外，二甲双胍降低了神经元中内质网应激相关蛋白的表达，并减少了小胶质细胞激活引发的炎症反应。进一步的机制分析表明，二甲双胍抑制了小胶质细胞中STING和NLRP3的表达和激活。这些结果揭示了二甲双胍改善下丘脑衰老的一种可能机制。
