FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis

Objective: Fibroblast growth factor 2 (FGF2) has been reported to play divergent roles in white adipogenic differentiation, however, whether it regulates thermogenesis of fat tissues remains largely unknown. We therefore aimed to investigate the effect of FGF2 on fat thermogenesis and elucidate the...

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Main Authors: Haifang Li, Xinzhi Zhang, Cheng Huang, Huan Liu, Qiang Zhang, Qianying Sun, Yanxin Jia, Shuang Liu, Mei Dong, Mengjie Hou, Yiming Liu, Hai Lin
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:Molecular Metabolism
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877821002052
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author Haifang Li
Xinzhi Zhang
Cheng Huang
Huan Liu
Qiang Zhang
Qianying Sun
Yanxin Jia
Shuang Liu
Mei Dong
Mengjie Hou
Yiming Liu
Hai Lin
author_facet Haifang Li
Xinzhi Zhang
Cheng Huang
Huan Liu
Qiang Zhang
Qianying Sun
Yanxin Jia
Shuang Liu
Mei Dong
Mengjie Hou
Yiming Liu
Hai Lin
author_sort Haifang Li
collection DOAJ
description Objective: Fibroblast growth factor 2 (FGF2) has been reported to play divergent roles in white adipogenic differentiation, however, whether it regulates thermogenesis of fat tissues remains largely unknown. We therefore aimed to investigate the effect of FGF2 on fat thermogenesis and elucidate the underlying mechanisms. Methods: FGF2-KO and wild-type (WT) mice were fed with chow diet and high-fat diet (HFD) for 14 weeks. The brown and white fat mass, thermogenic capability, respiratory exchange ratio, and hepatic fat deposition were determined. In vitro experiments were conducted to compare the thermogenic ability of FGF2-KO- with WT-derived brown and white adipocytes. Exogenous FGF2 was supplemented to in vitro-cultured WT brown and ISO-induced beige adipocytes. The FGFR inhibitor, PPARγ agonist, and PGC-1α expression lentivirus were used with the aid of technologies including Co-IP, ChIP, and luciferase reporter assay to elucidate the mechanisms underlying the FGF2 regulation of thermogenesis. Results: FGF2 gene disruption results in increased thermogenic capability in both brown and beige fat, supporting by increased UCP1 expression, enhanced respiratory exchange ratio, and elevated thermogenic potential in response to cold exposure. Thus, the deletion of FGF2 protects mice from high fat-induced adiposity and hepatic steatosis. Mechanistically, in vitro investigations indicated FGF2 acts in autocrine/paracrine fashions. Exogenous FGF2 supplementation inhibits both PGC-1α and PPARγ expression, leading to suppression of UCP1 expression in brown and beige adipocytes. Conclusions: These findings demonstrate that FGF2 is a novel thermogenic regulator, suggesting a viable potential strategy for using FGF2-selective inhibitors in combat adiposity and associated hepatic steatosis.
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spelling doaj.art-dbc999b6e08e44408b5f2a81e8a9ac902022-12-22T04:08:58ZengElsevierMolecular Metabolism2212-87782021-12-0154101358FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosisHaifang Li0Xinzhi Zhang1Cheng Huang2Huan Liu3Qiang Zhang4Qianying Sun5Yanxin Jia6Shuang Liu7Mei Dong8Mengjie Hou9Yiming Liu10Hai Lin11State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China; Corresponding author.State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaCollege of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaState Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, ChinaCollege of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China; Corresponding author.Objective: Fibroblast growth factor 2 (FGF2) has been reported to play divergent roles in white adipogenic differentiation, however, whether it regulates thermogenesis of fat tissues remains largely unknown. We therefore aimed to investigate the effect of FGF2 on fat thermogenesis and elucidate the underlying mechanisms. Methods: FGF2-KO and wild-type (WT) mice were fed with chow diet and high-fat diet (HFD) for 14 weeks. The brown and white fat mass, thermogenic capability, respiratory exchange ratio, and hepatic fat deposition were determined. In vitro experiments were conducted to compare the thermogenic ability of FGF2-KO- with WT-derived brown and white adipocytes. Exogenous FGF2 was supplemented to in vitro-cultured WT brown and ISO-induced beige adipocytes. The FGFR inhibitor, PPARγ agonist, and PGC-1α expression lentivirus were used with the aid of technologies including Co-IP, ChIP, and luciferase reporter assay to elucidate the mechanisms underlying the FGF2 regulation of thermogenesis. Results: FGF2 gene disruption results in increased thermogenic capability in both brown and beige fat, supporting by increased UCP1 expression, enhanced respiratory exchange ratio, and elevated thermogenic potential in response to cold exposure. Thus, the deletion of FGF2 protects mice from high fat-induced adiposity and hepatic steatosis. Mechanistically, in vitro investigations indicated FGF2 acts in autocrine/paracrine fashions. Exogenous FGF2 supplementation inhibits both PGC-1α and PPARγ expression, leading to suppression of UCP1 expression in brown and beige adipocytes. Conclusions: These findings demonstrate that FGF2 is a novel thermogenic regulator, suggesting a viable potential strategy for using FGF2-selective inhibitors in combat adiposity and associated hepatic steatosis.http://www.sciencedirect.com/science/article/pii/S2212877821002052Fibroblast growth factor 2 (FGF2)ThermogenesisBrown and beige fatPPARγPGC-1α
spellingShingle Haifang Li
Xinzhi Zhang
Cheng Huang
Huan Liu
Qiang Zhang
Qianying Sun
Yanxin Jia
Shuang Liu
Mei Dong
Mengjie Hou
Yiming Liu
Hai Lin
FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
Molecular Metabolism
Fibroblast growth factor 2 (FGF2)
Thermogenesis
Brown and beige fat
PPARγ
PGC-1α
title FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
title_full FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
title_fullStr FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
title_full_unstemmed FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
title_short FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
title_sort fgf2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis
topic Fibroblast growth factor 2 (FGF2)
Thermogenesis
Brown and beige fat
PPARγ
PGC-1α
url http://www.sciencedirect.com/science/article/pii/S2212877821002052
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