PMID- 32434959 OWN - NLM STAT- MEDLINE DCOM- 20210226 LR - 20231213 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 12 IP - 9 DP - 2020 May 13 TI - Soy isoflavones improve the oxidative stress induced hypothalamic inflammation and apoptosis in high fat diet-induced obese male mice through PGC1-alpha pathway. PG - 8710-8727 LID - 10.18632/aging.103197 [doi] AB - Obesity is a common metabolic disorder that increases the risk of many diseases, such as type II diabetes, hypertension, cardiovascular disease. Hypothalamus plays a very important role in the progression of obesity, and many studies reveal that hypothalamic injures are implicated in obesity processes. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through improving the hypothalamic inflammation and apoptosis, which are induced by oxidative stress. Also, our in vitro studies demonstrate that daidzein and genistein, common ingredients of soy isoflavones, could protect hypothalamic N42 cells against palmitic acid induced oxidative stress and apoptosis. Moreover, the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-alpha), which plays a role in oxidative defense, is increased after soy isoflavone treatment in vivo and in vitro, suggesting an improved effect of soy isoflavones on hypothalamic antioxidant defense is mediated by PGC-1alpha. Our study reveals a potential mechanism of soy isoflavones regulating oxidative stress induced hypothalamic inflammation and cellular apoptosis, which will be important for obesity treatment. FAU - Pang, Dejiang AU - Pang D AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Neuroscience and Metabolism Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, P.R. China. FAU - Yang, Chengcheng AU - Yang C AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Luo, Qihui AU - Luo Q AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Li, Chao AU - Li C AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Liu, Wentao AU - Liu W AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Li, Lixia AU - Li L AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Zou, Yuanfeng AU - Zou Y AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Feng, Bin AU - Feng B AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Chen, Zhengli AU - Chen Z AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. FAU - Huang, Chao AU - Huang C AD - Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. AD - Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200513 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Antioxidants) RN - 0 (Isoflavones) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, mouse) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Apoptosis/drug effects MH - Diet, High-Fat/adverse effects MH - Hypothalamus/*drug effects/metabolism MH - Inflammation/drug therapy/metabolism MH - Isoflavones/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Obesity/*drug therapy/etiology/metabolism/pathology MH - Oxidative Stress/*drug effects MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*genetics MH - Glycine max/chemistry PMC - PMC7244041 OTO - NOTNLM OT - PGC1-alpha OT - inflammation OT - obesity OT - oxidative stress OT - soy isoflavones COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest. EDAT- 2020/05/22 06:00 MHDA- 2021/02/27 06:00 PMCR- 2020/05/15 CRDT- 2020/05/22 06:00 PHST- 2019/11/02 00:00 [received] PHST- 2020/04/16 00:00 [accepted] PHST- 2020/05/22 06:00 [entrez] PHST- 2020/05/22 06:00 [pubmed] PHST- 2021/02/27 06:00 [medline] PHST- 2020/05/15 00:00 [pmc-release] AID - 103197 [pii] AID - 10.18632/aging.103197 [doi] PST - ppublish SO - Aging (Albany NY). 2020 May 13;12(9):8710-8727. doi: 10.18632/aging.103197. Epub 2020 May 13.