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Food Science and Human Wellness 2022, 11(2): 405-417 https://doi.org/10.1016/j.fshw.2021.11.022
Research Article | Open Access | Issue | Published: 25 November 2021

Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4

Show Author's Information Hui Gaoa,b,1( ),  Kunming Tianc,1,  Xiaojun Fengd,  Mengqing Yana,  Chen Gaoa,  Yisheng Jianga,  Chenhao Zhua,  Huzhe Zhua,  Xueping Liue( ),  Yingfu Pengb( )
Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, China
Department of Pharmacology, School of Medicine, Jishou University, Jishou 416000, China
Department of Environmental Toxicity, Zunyi Medical University, Zunyi 563006, China
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230002, China
Department of Pharmacology, School of Medicine, GuangXi University of science and Technology, Liuzhou 545006, China

1 These authors contributed equally to this work. Peer review under responsibility of KeAi Communications Co., Ltd.]]>

Keywords:
FFA2, Cardiac hypertrophy, GATA4, STAT3, ERK1/2
Cite this article:
Gao H, Tian K, Feng X, et al. Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4. Food Science and Human Wellness, 2022, 11(2): 405-417. https://doi.org/10.1016/j.fshw.2021.11.022
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Abstract Full text About this article

Free fatty acids (FFAs) play important roles in cardiovascular disease. Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body. Free fatty acid receptor 2 (FFA2) can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation. Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy, we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy. This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro. FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro, which was further strengthened by FFA2 overexpression, suggesting that FFA2 might contribute to cardiomyocyte hypertrophy. Furthermore, 4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3, which were inhibited by an ERK1/2 inhibitor, and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB. Taken together, these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2, providing a potential new target for therapy.


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About this article

Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4

Show Author's information Hui Gaoa,b,1( ), Kunming Tianc,1, Xiaojun Fengd, Mengqing Yana, Chen Gaoa, Yisheng Jianga, Chenhao Zhua, Huzhe Zhua, Xueping Liue( ), Yingfu Pengb( )
Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, China
Department of Pharmacology, School of Medicine, Jishou University, Jishou 416000, China
Department of Environmental Toxicity, Zunyi Medical University, Zunyi 563006, China
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230002, China
Department of Pharmacology, School of Medicine, GuangXi University of science and Technology, Liuzhou 545006, China

1 These authors contributed equally to this work. Peer review under responsibility of KeAi Communications Co., Ltd.]]>

Abstract

Free fatty acids (FFAs) play important roles in cardiovascular disease. Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body. Free fatty acid receptor 2 (FFA2) can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation. Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy, we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy. This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro. FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro, which was further strengthened by FFA2 overexpression, suggesting that FFA2 might contribute to cardiomyocyte hypertrophy. Furthermore, 4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3, which were inhibited by an ERK1/2 inhibitor, and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB. Taken together, these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2, providing a potential new target for therapy.

Keywords: FFA2, Cardiac hypertrophy, GATA4, STAT3, ERK1/2

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Received: 14 February 2021
Revised: 04 May 2021
Accepted: 05 May 2021
Published: 25 November 2021
Issue date: March 2022

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© 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81760058, 81560059, 81660042, 31800891), the Scientific Research Project of Health and Family Planning Commission of Hunan Province (No. C2017025), the Project of Medical and Health Science and Technology of Shaoxing City (No. 2020A13063) and the Startup Fund for Research of Shaoxing University (No. 20205021).

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