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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 ameliorates metabolic disorders in high-fat diet-induced obesity C57BL/6 mice.(a) Body weight gain. (b) Mass of white adipose tissue. (c) Food intake amount. (d) Fecal triglyceride level. (e) Body temperature. (f) Fasting blood glucose level. (g) Glucose tolerance test (GTT). (h) Insulin tolerance test (ITT). (i) Serum insulin content. (j) Serum leptin content. (k) Serum adiponeciton content. (l) Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c). (m) Free fatty acid (FFA) level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. HF group.
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f2: PPT ameliorates metabolic disorders in high-fat diet-induced obesity C57BL/6 mice.(a) Body weight gain. (b) Mass of white adipose tissue. (c) Food intake amount. (d) Fecal triglyceride level. (e) Body temperature. (f) Fasting blood glucose level. (g) Glucose tolerance test (GTT). (h) Insulin tolerance test (ITT). (i) Serum insulin content. (j) Serum leptin content. (k) Serum adiponeciton content. (l) Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c). (m) Free fatty acid (FFA) level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. HF group.

Mentions: Previous studies have demonstrated that a moderate reduction of PPARγ activity may reduce the risk for the development of obesity and type 2 diabetes. Since PPT inhibits adipocyte differentiation in vitro, we asked whether PPT has the effect on body weight changes in obese C57BL/6 mice. The mice were placed on a high-fat diet for 3-month to induce obesity, and then the obese mice were divided into two groups and fed with HF mixed with 1 g/kg PPT or HF diet alone for 4 weeks. As shown in Fig. 2a, the mice fed with PPT supplementation displayed much lower body weight than control DIO mice at the end of treatment. In addition, electronic scanning microscopy assays showed that the size of adipocytes in WAT of PPT-treated mice was reduced compared to that of the DIO mice (Fig. 2b). PPT treatment did not alter the food intake and the fecal TG in mice (Fig. 2c and 2d). Nevertheless, PPT-treated mice showed a significantly higher body temperature compared to the DIO mice (Fig. 2e), indicating that PPT may enhance the energy expenditure.


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 ameliorates metabolic disorders in high-fat diet-induced obesity C57BL/6 mice.(a) Body weight gain. (b) Mass of white adipose tissue. (c) Food intake amount. (d) Fecal triglyceride level. (e) Body temperature. (f) Fasting blood glucose level. (g) Glucose tolerance test (GTT). (h) Insulin tolerance test (ITT). (i) Serum insulin content. (j) Serum leptin content. (k) Serum adiponeciton content. (l) Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c). (m) Free fatty acid (FFA) level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. HF group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: PPT ameliorates metabolic disorders in high-fat diet-induced obesity C57BL/6 mice.(a) Body weight gain. (b) Mass of white adipose tissue. (c) Food intake amount. (d) Fecal triglyceride level. (e) Body temperature. (f) Fasting blood glucose level. (g) Glucose tolerance test (GTT). (h) Insulin tolerance test (ITT). (i) Serum insulin content. (j) Serum leptin content. (k) Serum adiponeciton content. (l) Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c). (m) Free fatty acid (FFA) level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. HF group.
Mentions: Previous studies have demonstrated that a moderate reduction of PPARγ activity may reduce the risk for the development of obesity and type 2 diabetes. Since PPT inhibits adipocyte differentiation in vitro, we asked whether PPT has the effect on body weight changes in obese C57BL/6 mice. The mice were placed on a high-fat diet for 3-month to induce obesity, and then the obese mice were divided into two groups and fed with HF mixed with 1 g/kg PPT or HF diet alone for 4 weeks. As shown in Fig. 2a, the mice fed with PPT supplementation displayed much lower body weight than control DIO mice at the end of treatment. In addition, electronic scanning microscopy assays showed that the size of adipocytes in WAT of PPT-treated mice was reduced compared to that of the DIO mice (Fig. 2b). PPT treatment did not alter the food intake and the fecal TG in mice (Fig. 2c and 2d). Nevertheless, PPT-treated mice showed a significantly higher body temperature compared to the DIO mice (Fig. 2e), indicating that PPT may enhance the energy expenditure.

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