Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis
Abstract GLP‐1 is a vital candidate for stimulating insulin secretion in a glucose‐dependent manner, reducing body weight and eliminating nonalcoholic fatty liver disease with few side effects. Therefore, elevating GLP‐1 secretion and antagonizing the enzymatic cleavage by DPP4 are the main directio...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Food Frontiers |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/fft2.329 |
| _version_ | 1797257806597849088 |
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| author | Yuxuan An Lichao Zhang Xiaxia Fan Kaili Cui Shuiling He Pengyu Ji Jinmiao Tian Zhuoyu Li |
| author_facet | Yuxuan An Lichao Zhang Xiaxia Fan Kaili Cui Shuiling He Pengyu Ji Jinmiao Tian Zhuoyu Li |
| author_sort | Yuxuan An |
| collection | DOAJ |
| description | Abstract GLP‐1 is a vital candidate for stimulating insulin secretion in a glucose‐dependent manner, reducing body weight and eliminating nonalcoholic fatty liver disease with few side effects. Therefore, elevating GLP‐1 secretion and antagonizing the enzymatic cleavage by DPP4 are the main direction of GLP‐1‐based drug development. The present study implies that ferulic acid (FA) treatment increased the serum GLP‐1 level in diet‐induced obesity mice. The binding of FA to GLP‐1 effectively prevented the enzymatic cleavage of GLP‐1 by DPP4, which led to the effective elimination of hepatic cellular lipids by GLP‐1 in vitro. Furthermore, studies of fluorescence titration and molecular simulation showed that the combination ratio of FA and GLP‐1 was 1:1, and FA could enhance the stability of GLP‐1 through van der Waals force and electrostatic force binding to GLP‐1. In turn, it increased the level of endogenous GLP‐1. More importantly, data from mass spectrometry analysis revealed that FA bound to GLN‐17, ALA‐18, or ALA‐19 sites of GLP‐1 differently. In addition, after binding to FA, the α‐helix in GLP‐1 did not change significantly, and the biological activity of GLP‐1 was unaffected. These results highlight that FA‐rich food, such as millet and oats, is an excellent source of dietary intervention for metabolic disorders. |
| first_indexed | 2024-04-24T22:43:30Z |
| format | Article |
| id | doaj.art-4eaf3e96abe5404f8ef5459035b3ba3c |
| institution | Directory Open Access Journal |
| issn | 2643-8429 |
| language | English |
| last_indexed | 2024-04-24T22:43:30Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Food Frontiers |
| spelling | doaj.art-4eaf3e96abe5404f8ef5459035b3ba3c2024-03-18T16:46:15ZengWileyFood Frontiers2643-84292024-03-015269170710.1002/fft2.329Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosisYuxuan An0Lichao Zhang1Xiaxia Fan2Kaili Cui3Shuiling He4Pengyu Ji5Jinmiao Tian6Zhuoyu Li7Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaInstitutes of Biomedical Sciences Shanxi University Taiyuan ChinaInstitute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaInstitute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaInstitute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaInstitute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaInstitute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaInstitute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education Shanxi University Taiyuan ChinaAbstract GLP‐1 is a vital candidate for stimulating insulin secretion in a glucose‐dependent manner, reducing body weight and eliminating nonalcoholic fatty liver disease with few side effects. Therefore, elevating GLP‐1 secretion and antagonizing the enzymatic cleavage by DPP4 are the main direction of GLP‐1‐based drug development. The present study implies that ferulic acid (FA) treatment increased the serum GLP‐1 level in diet‐induced obesity mice. The binding of FA to GLP‐1 effectively prevented the enzymatic cleavage of GLP‐1 by DPP4, which led to the effective elimination of hepatic cellular lipids by GLP‐1 in vitro. Furthermore, studies of fluorescence titration and molecular simulation showed that the combination ratio of FA and GLP‐1 was 1:1, and FA could enhance the stability of GLP‐1 through van der Waals force and electrostatic force binding to GLP‐1. In turn, it increased the level of endogenous GLP‐1. More importantly, data from mass spectrometry analysis revealed that FA bound to GLN‐17, ALA‐18, or ALA‐19 sites of GLP‐1 differently. In addition, after binding to FA, the α‐helix in GLP‐1 did not change significantly, and the biological activity of GLP‐1 was unaffected. These results highlight that FA‐rich food, such as millet and oats, is an excellent source of dietary intervention for metabolic disorders.https://doi.org/10.1002/fft2.329ferulic acidGLP‐1hepatic steatosis |
| spellingShingle | Yuxuan An Lichao Zhang Xiaxia Fan Kaili Cui Shuiling He Pengyu Ji Jinmiao Tian Zhuoyu Li Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis Food Frontiers ferulic acid GLP‐1 hepatic steatosis |
| title | Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis |
| title_full | Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis |
| title_fullStr | Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis |
| title_full_unstemmed | Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis |
| title_short | Ferulic acid reduces GLP‐1 degradation to ameliorate diet‐induced obesity‐associated hepatic steatosis |
| title_sort | ferulic acid reduces glp 1 degradation to ameliorate diet induced obesity associated hepatic steatosis |
| topic | ferulic acid GLP‐1 hepatic steatosis |
| url | https://doi.org/10.1002/fft2.329 |
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