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Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α

BACKGROUND: Promoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced...

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Autores principales: Leng, Qingyang, Zhou, Jianhua, Li, Chang, Xu, Yanhong, Liu, Lu, Zhu, Yi, Yang, Ying, Zhang, Hongli, Li, Xiaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188085/
https://www.ncbi.nlm.nih.gov/pubmed/35690863
http://dx.doi.org/10.1186/s12986-022-00672-6
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author Leng, Qingyang
Zhou, Jianhua
Li, Chang
Xu, Yanhong
Liu, Lu
Zhu, Yi
Yang, Ying
Zhang, Hongli
Li, Xiaohua
author_facet Leng, Qingyang
Zhou, Jianhua
Li, Chang
Xu, Yanhong
Liu, Lu
Zhu, Yi
Yang, Ying
Zhang, Hongli
Li, Xiaohua
author_sort Leng, Qingyang
collection PubMed
description BACKGROUND: Promoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced obesity through promoting the browning of WAT. METHODS: Male C57BL/6 J mice were received a high-fat diet (HFD) to induce obesity and subsequently were treated with DHM (100 mg/kg/day) or vehicle for 4 weeks. The effects of DHM on weight reduction and metabolic phenotype improvement were observed in the mice. The expression of genes and protein involved in browning of WAT were assessed in inguinal WAT (iWAT) of the mice. Then, the effect of DHM on the inducing browning program was verified in adipocytes differentiated from stromal vascular fraction (SVF) cells of mouse iWAT. Finally, the mechanism by which DHM improves the browning of WAT was explored using RNA-seq and luciferase reporter assay. RESULTS: We find that DHM reduces body weight, decreases WAT mass, improves glucose and lipid metabolic disorders, and ameliorates hepatic steatosis in diet-induced obese (DIO) mice. Further studies show that DHM induces WAT browning, which is manifested by increased expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and enhanced mitochondrial activity in iWAT and primary adipocytes. In addition, we also find that DHM enhances interferon regulatory factor 4 (IRF4) expression, which is a key transcriptional regulator of PGC-1α. CONCLUSION: Our findings identify that DHM prevents obesity by inducing the browning of WAT through the upregulation of IRF4/PGC-1α, which may have potential therapeutic implications for the treatment of obesity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12986-022-00672-6.
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spelling pubmed-91880852022-06-12 Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α Leng, Qingyang Zhou, Jianhua Li, Chang Xu, Yanhong Liu, Lu Zhu, Yi Yang, Ying Zhang, Hongli Li, Xiaohua Nutr Metab (Lond) Research BACKGROUND: Promoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced obesity through promoting the browning of WAT. METHODS: Male C57BL/6 J mice were received a high-fat diet (HFD) to induce obesity and subsequently were treated with DHM (100 mg/kg/day) or vehicle for 4 weeks. The effects of DHM on weight reduction and metabolic phenotype improvement were observed in the mice. The expression of genes and protein involved in browning of WAT were assessed in inguinal WAT (iWAT) of the mice. Then, the effect of DHM on the inducing browning program was verified in adipocytes differentiated from stromal vascular fraction (SVF) cells of mouse iWAT. Finally, the mechanism by which DHM improves the browning of WAT was explored using RNA-seq and luciferase reporter assay. RESULTS: We find that DHM reduces body weight, decreases WAT mass, improves glucose and lipid metabolic disorders, and ameliorates hepatic steatosis in diet-induced obese (DIO) mice. Further studies show that DHM induces WAT browning, which is manifested by increased expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and enhanced mitochondrial activity in iWAT and primary adipocytes. In addition, we also find that DHM enhances interferon regulatory factor 4 (IRF4) expression, which is a key transcriptional regulator of PGC-1α. CONCLUSION: Our findings identify that DHM prevents obesity by inducing the browning of WAT through the upregulation of IRF4/PGC-1α, which may have potential therapeutic implications for the treatment of obesity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12986-022-00672-6. BioMed Central 2022-06-11 /pmc/articles/PMC9188085/ /pubmed/35690863 http://dx.doi.org/10.1186/s12986-022-00672-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Leng, Qingyang
Zhou, Jianhua
Li, Chang
Xu, Yanhong
Liu, Lu
Zhu, Yi
Yang, Ying
Zhang, Hongli
Li, Xiaohua
Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
title Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
title_full Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
title_fullStr Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
title_full_unstemmed Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
title_short Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
title_sort dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating irf4/pgc-1α
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188085/
https://www.ncbi.nlm.nih.gov/pubmed/35690863
http://dx.doi.org/10.1186/s12986-022-00672-6
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