Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance. Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia. Ginsenoside is a natural active component in Panax ginseng C.A. Meyer, and some of them enhance...
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Format: | Article |
Language: | English |
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Tsinghua University Press
2023-11-01
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Series: | Food Science and Human Wellness |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023000770 |
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author | Yuhan Meng Weili Li Chenxing Hu Si Chen Haiyang Li Feifei Bai Lujuan Zheng Ye Yuan Yuying Fan Yifa Zhou |
author_facet | Yuhan Meng Weili Li Chenxing Hu Si Chen Haiyang Li Feifei Bai Lujuan Zheng Ye Yuan Yuying Fan Yifa Zhou |
author_sort | Yuhan Meng |
collection | DOAJ |
description | Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance. Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia. Ginsenoside is a natural active component in Panax ginseng C.A. Meyer, and some of them enhance thermogenesis. However, there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis. Using thermogenic protein uncoupling protein 1 (UCP1)-luciferase reporter assay, we identified ginsenoside F1 as a novel UCP1 activator in the ginsenosides library. Using pull down assay and inhibitor interference, we found F1 binds to β3-adrenergic receptors (β3-AR) to enhance UCP1 expression via cAMP/PKA/CREB pathway. We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice, including body weight, body composition and energy expenditure. The results of proteomics showed that F1 significantly up-regulated thermogenesis proteins and lipolytic proteins, but down-regulated fatty acid synthesis proteins. Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifically by promoting the browning of white adipose tissue in obese mice. Additionally, ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes, and shows a stronger mitochondria respiration ability than norepinephrine. These findings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance. |
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spelling | doaj.art-e97002b356ec407a93f6642afaa74f822023-09-03T09:56:32ZengTsinghua University PressFood Science and Human Wellness2213-45302023-11-0112620612072Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistanceYuhan Meng0Weili Li1Chenxing Hu2Si Chen3Haiyang Li4Feifei Bai5Lujuan Zheng6Ye Yuan7Yuying Fan8Yifa Zhou9Engineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaEngineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaCorresponding authors at: School of Life Sciences, Northeast Normal University, Changchun 130024, China; Engineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaCorresponding authors at: School of Life Sciences, Northeast Normal University, Changchun 130024, China; Engineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, ChinaObesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance. Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia. Ginsenoside is a natural active component in Panax ginseng C.A. Meyer, and some of them enhance thermogenesis. However, there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis. Using thermogenic protein uncoupling protein 1 (UCP1)-luciferase reporter assay, we identified ginsenoside F1 as a novel UCP1 activator in the ginsenosides library. Using pull down assay and inhibitor interference, we found F1 binds to β3-adrenergic receptors (β3-AR) to enhance UCP1 expression via cAMP/PKA/CREB pathway. We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice, including body weight, body composition and energy expenditure. The results of proteomics showed that F1 significantly up-regulated thermogenesis proteins and lipolytic proteins, but down-regulated fatty acid synthesis proteins. Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifically by promoting the browning of white adipose tissue in obese mice. Additionally, ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes, and shows a stronger mitochondria respiration ability than norepinephrine. These findings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.http://www.sciencedirect.com/science/article/pii/S2213453023000770Ginsenoside F1Uncoupling protein 1β3-Adrenergic receptorsWhite adipose tissue browningInsulin resistance |
spellingShingle | Yuhan Meng Weili Li Chenxing Hu Si Chen Haiyang Li Feifei Bai Lujuan Zheng Ye Yuan Yuying Fan Yifa Zhou Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance Food Science and Human Wellness Ginsenoside F1 Uncoupling protein 1 β3-Adrenergic receptors White adipose tissue browning Insulin resistance |
title | Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance |
title_full | Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance |
title_fullStr | Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance |
title_full_unstemmed | Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance |
title_short | Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance |
title_sort | ginsenoside f1 administration promotes ucp1 dependent fat browning and ameliorates obesity associated insulin resistance |
topic | Ginsenoside F1 Uncoupling protein 1 β3-Adrenergic receptors White adipose tissue browning Insulin resistance |
url | http://www.sciencedirect.com/science/article/pii/S2213453023000770 |
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