Journal of Clinical Toxicology
Open Access
ISSN: 2161-0495
+44 1478 350008
ISSN: 2161-0495
+44 1478 350008
Chunxu Hai, Xin Wang and Xiaodi Zhang
Fourth Military Medical University, China
Posters & Accepted Abstracts: J Clinic Toxicol
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 PPAR�?³ and its target gene expression both in differentiated 3T3-L1 adipocytes and fat tissues in HF diet-fed mice. Overexpression of PPAR�?³ suppressed DSG-inhibited adipocyte differentiation. DSG significantly increased nuclear expression of ER�?². Inhibition of ER�?² significantly suppressed DSG-exerted suppression of adipocyte differentiation and PPAR�?³ expression. In response to DSG stimulation, ER�?² bound with RXR�?± and dissociated RXR�?± from PPAR�?³, leading to the reduction of transcriptional activity of PPAR�?³. These data provide new insight into the mechanisms underlying the inhibitory effect of DSG on adipocyte differentiation and demonstrate that ER�?²-exerted regulation of PPAR�?³ expression and activity is critical for DSG-inhibited adipocyte differentiation.
Email: cx-hai@fmmu.edu.cn