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Protopanaxatriol, a novel PPARγ antagonist from Panax ginseng, alleviates steatosis in mice.

Zhang Y, Yu L, Cai W, Fan S, Feng L, Ji G, Huang C - Sci Rep (2014)

Bottom Line: Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis.TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study.Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.

ABSTRACT
Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis. Ginseng has been used as food and traditional herbal medicine for the treatment of various metabolic diseases. However, the molecular mechanisms how ginseng and its components participate in the regulation of lipogenesis are still largely unclear. Here, we identified that protopanaxatriol (PPT), a major ginseng constituent, inhibited rosiglitazone-supported adipocyte differentiation of 3T3-L1 cells by repressing the expression of lipogenesis-related gene expression. In high-fat diet-induced obesity (DIO) mice, PPT reduced body weight and serum lipid levels, improved insulin resistance, as well as morphology and lipid accumulation, particular macrovesicular steatosis, in the livers. These effects were confirmed with genetically obese ob/ob mice. A reporter gene assay showed that PPT specifically inhibited the transactivity of PPARγ, but not PPAR α, β/δ and LXR α, β. TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study. Our data demonstrate that PPT is a novel PPARγ antagonist. The inhibition of PPARγ activity could be a promising therapy for obesity and steatosis. Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

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PPT inhibits the mRNA expression of the PPARγ target genes.(a) The mRNA expression level of the thermogenic genes in BAT in DIO mice. (b) The mRNA expression level of the UCP-1 in WAT of DIO mice. (c)- (d) RT-PCR analysis of gene expression in liver tissue (b) and WAT (c) of DIO mice (n = 6). (e)- (f) RT-PCR analysis of gene expression in liver tissue (e) and WAT (f) of ob/ob mice (n = 6). (g) The mRNA expression level of the inflammatory genes in WAT of DIO mice. Data are presented as means ± SEM (n = 6). *P<0.05, **P<0.01vs. ob/ob mice.
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f7: PPT inhibits the mRNA expression of the PPARγ target genes.(a) The mRNA expression level of the thermogenic genes in BAT in DIO mice. (b) The mRNA expression level of the UCP-1 in WAT of DIO mice. (c)- (d) RT-PCR analysis of gene expression in liver tissue (b) and WAT (c) of DIO mice (n = 6). (e)- (f) RT-PCR analysis of gene expression in liver tissue (e) and WAT (f) of ob/ob mice (n = 6). (g) The mRNA expression level of the inflammatory genes in WAT of DIO mice. Data are presented as means ± SEM (n = 6). *P<0.05, **P<0.01vs. ob/ob mice.

Mentions: Consistent with the increase of body temperature, the expression of uncoupling protein (UCP)-1, UCP-2 and UCP-3 genes, involved in energy dissipation and adoptive thermogenesis in brown adipose tissue (BAT), was enhanced in the BAT of PPT-treated mice (Fig. 7a). The other adipose tissue involving in the heat production and energy expenditure is beige adipose in WAT. The elevated expression of UCP-1 is a key feature for browning of WAT40. Interestingly, PPT treatment increased the expression of UCP-1 in WAT (Fig. 7b). These data suggest that PPT may promote the energy expenditure, which in turn, could also reduce adiposity.


Protopanaxatriol, a novel PPARγ antagonist from Panax ginseng, alleviates steatosis in mice.

Zhang Y, Yu L, Cai W, Fan S, Feng L, Ji G, Huang C - Sci Rep (2014)

PPT inhibits the mRNA expression of the PPARγ target genes.(a) The mRNA expression level of the thermogenic genes in BAT in DIO mice. (b) The mRNA expression level of the UCP-1 in WAT of DIO mice. (c)- (d) RT-PCR analysis of gene expression in liver tissue (b) and WAT (c) of DIO mice (n = 6). (e)- (f) RT-PCR analysis of gene expression in liver tissue (e) and WAT (f) of ob/ob mice (n = 6). (g) The mRNA expression level of the inflammatory genes in WAT of DIO mice. Data are presented as means ± SEM (n = 6). *P<0.05, **P<0.01vs. ob/ob mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260220&req=5

f7: PPT inhibits the mRNA expression of the PPARγ target genes.(a) The mRNA expression level of the thermogenic genes in BAT in DIO mice. (b) The mRNA expression level of the UCP-1 in WAT of DIO mice. (c)- (d) RT-PCR analysis of gene expression in liver tissue (b) and WAT (c) of DIO mice (n = 6). (e)- (f) RT-PCR analysis of gene expression in liver tissue (e) and WAT (f) of ob/ob mice (n = 6). (g) The mRNA expression level of the inflammatory genes in WAT of DIO mice. Data are presented as means ± SEM (n = 6). *P<0.05, **P<0.01vs. ob/ob mice.
Mentions: Consistent with the increase of body temperature, the expression of uncoupling protein (UCP)-1, UCP-2 and UCP-3 genes, involved in energy dissipation and adoptive thermogenesis in brown adipose tissue (BAT), was enhanced in the BAT of PPT-treated mice (Fig. 7a). The other adipose tissue involving in the heat production and energy expenditure is beige adipose in WAT. The elevated expression of UCP-1 is a key feature for browning of WAT40. Interestingly, PPT treatment increased the expression of UCP-1 in WAT (Fig. 7b). These data suggest that PPT may promote the energy expenditure, which in turn, could also reduce adiposity.

Bottom Line: Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis.TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study.Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.

ABSTRACT
Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis. Ginseng has been used as food and traditional herbal medicine for the treatment of various metabolic diseases. However, the molecular mechanisms how ginseng and its components participate in the regulation of lipogenesis are still largely unclear. Here, we identified that protopanaxatriol (PPT), a major ginseng constituent, inhibited rosiglitazone-supported adipocyte differentiation of 3T3-L1 cells by repressing the expression of lipogenesis-related gene expression. In high-fat diet-induced obesity (DIO) mice, PPT reduced body weight and serum lipid levels, improved insulin resistance, as well as morphology and lipid accumulation, particular macrovesicular steatosis, in the livers. These effects were confirmed with genetically obese ob/ob mice. A reporter gene assay showed that PPT specifically inhibited the transactivity of PPARγ, but not PPAR α, β/δ and LXR α, β. TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study. Our data demonstrate that PPT is a novel PPARγ antagonist. The inhibition of PPARγ activity could be a promising therapy for obesity and steatosis. Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

Show MeSH
Related in: MedlinePlus