Effect of diosgenin on metabolic dysfunction: Role of ERβ in the regulation of PPARγ

Journal Article · Tue Dec 01 04:00:00 EST 2015 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2015.09.015· OSTI ID:22687834

Wang, Xin ^[1]; Liu, Jun ^[2]; Long, Zi; Sun, Quangui ^[3]; Liu, Ying; Wang, Lele; Zhang, Xiaodi ^[1]; Hai, Chunxu ^[1]

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1. 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)
2. Department of Orthopedics, Lanzhou General Hospital of PLA, South Binhe Road, No. 333, Lanzhou 730050 (China)
3. The First Student Brigade, Fourth Military Medical University, Xi'an, Shaanxi, 710032 (China)

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. - Highlights: • Diosgenin (DSG) attenuated metabolic dysfunction in high fat (HF) diet-fed mice. • DSG reduced oxidative stress and lipid accumulation in HF diet-fed mice. • DSG inhibited 3T3-L1 adipocyte differentiation and reduced adipocyte size. • DSG induced the binding of ERβ with RXRα. • DSG-induced activation of ERβ dissociated RXRα from PPARγ and reduced PPARγ activity.

• OSTI ID: 22687834
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 289; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
BLOOD
DIET
ESTROGENS
FATS
GLUCOSE
HYDROFLUORIC ACID
INHIBITION
INSULIN
LIPIDS
MICE
OXIDATION
RECEPTORS
REGULATIONS