title: Effect of diosgenin on metabolic dysfunction: Role of ERβ in the regulation of PPARγ.
abstract: The present study was designed to investigate the effect of diosgenin (DSG) on metabolic dysfunction and to elucidate the possible molecular mechanisms. High fat (HF) diet-fed mice and 3T3-L1 preadipocytes was used to evaluate the effect of DSG. We showed that DSG attenuated metabolic dysfunction in HF diet-fed mice, as evidenced by reduction of blood glucose level and improvement of glucose and insulin intolerance. DSG ameliorated oxidative stress, reduced body weight, fat pads, and systematic lipid profiles and attenuated lipid accumulation. DSG inhibited 3T3-L1 adipocyte differentiation and reduced adipocyte size through regulating key factors. DSG inhibited PPARγ and its target gene expression both in differentiated 3T3-L1 adipocytes and fat tissues in HF diet-fed mice. Overexpression of PPARγ suppressed DSG-inhibited adipocyte differentiation. DSG significantly increased nuclear expression of ERβ. Inhibition of ERβ significantly suppressed DSG-exerted suppression of adipocyte differentiation and PPARγ expression. In response to DSG stimulation, ERβ bound with RXRα and dissociated RXRα from PPARγ, leading to the reduction of transcriptional activity of PPARγ. These data provide new insight into the mechanisms underlying the inhibitory effect of DSG on adipocyte differentiation and demonstrate that ERβ-exerted regulation of PPARγ expression and activity is critical for DSG-inhibited adipocyte differentiation.
authors.affiliation: Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: xinwang@fmmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Lanzhou General Hospital of PLA, South Binhe Road, No. 333, Lanzhou 730050, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: The First Student Brigade, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Long
authors.affiliation: The First Student Brigade, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Quangui
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lele
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: cx-hai@fmmu.edu.cn.
authors.forename: Chunxu
authors.initials: C
authors.lastname: Hai
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D004144:Diosgenin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D047629:Estrogen Receptor beta; D007328:Insulin; D008055:Lipids; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D047490:Retinoid X Receptor alpha; D004144:Diosgenin
keywords: Adipocyte differentiation; Diosgenin; Estrogen receptor β; Metabolic dysfunction; Peroxisome proliferator-activated receptor γ; Retinoid X receptor α