Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4
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 sh...
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Tsinghua University Press
2022-03-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221345302100118X |
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| author | Hui Gao Kunming Tian Xiaojun Feng Mengqing Yan Chen Gao Yisheng Jiang Chenhao Zhu Huzhe Zhu Xueping Liu Yingfu Peng |
| author_facet | Hui Gao Kunming Tian Xiaojun Feng Mengqing Yan Chen Gao Yisheng Jiang Chenhao Zhu Huzhe Zhu Xueping Liu Yingfu Peng |
| author_sort | Hui Gao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ef17cf5f6f324c03a9febe2ebb425924 |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2022-03-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-ef17cf5f6f324c03a9febe2ebb4259242025-02-03T10:39:04ZengTsinghua University PressFood Science and Human Wellness2213-45302022-03-01112405417Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4Hui Gao0Kunming Tian1Xiaojun Feng2Mengqing Yan3Chen Gao4Yisheng Jiang5Chenhao Zhu6Huzhe Zhu7Xueping Liu8Yingfu Peng9Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, China; Department of Pharmacology, School of Medicine, Jishou University, Jishou 416000, China; Corresponding author.Department of Environmental Toxicity, Zunyi Medical University, Zunyi 563006, ChinaThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230002, ChinaDepartment of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, ChinaDepartment of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, ChinaDepartment of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, ChinaDepartment of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, ChinaDepartment of Pharmacology, School of Medicine, Shaoxing University, Shaoxing 312000, ChinaDepartment of Pharmacology, School of Medicine, GuangXi University of science and Technology, Liuzhou 545006, China; Corresponding author.Department of Pharmacology, School of Medicine, Jishou University, Jishou 416000, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S221345302100118XFFA2Cardiac hypertrophyGATA4STAT3ERK1/2 |
| spellingShingle | Hui Gao Kunming Tian Xiaojun Feng Mengqing Yan Chen Gao Yisheng Jiang Chenhao Zhu Huzhe Zhu Xueping Liu Yingfu Peng Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4 Food Science and Human Wellness FFA2 Cardiac hypertrophy GATA4 STAT3 ERK1/2 |
| title | Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4 |
| title_full | Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4 |
| title_fullStr | Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4 |
| title_full_unstemmed | Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4 |
| title_short | Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4 |
| title_sort | free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating stat3 and gata4 |
| topic | FFA2 Cardiac hypertrophy GATA4 STAT3 ERK1/2 |
| url | http://www.sciencedirect.com/science/article/pii/S221345302100118X |
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