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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Main Authors: Yuhan Meng, Weili Li, Chenxing Hu, Si Chen, Haiyang Li, Feifei Bai, Lujuan Zheng, Ye Yuan, Yuying Fan, Yifa Zhou
Format: Article
Language:English
Published: Tsinghua University Press 2023-11-01
Series:Food Science and Human Wellness
Subjects:
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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