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Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation
Purpose: N (6)-methyladenosine (m(6)A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m(6)A mRNA methylation remains unknown. Here, the objective of this study was to investi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845411/ https://www.ncbi.nlm.nih.gov/pubmed/33519432 http://dx.doi.org/10.3389/fphar.2020.568006 |
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author | Wu, Jiamin Li, Yi Yu, Jiayao Gan, Zhending Wei, Wenyao Wang, Chao Zhang, Lili Wang, Tian Zhong, Xiang |
author_facet | Wu, Jiamin Li, Yi Yu, Jiayao Gan, Zhending Wei, Wenyao Wang, Chao Zhang, Lili Wang, Tian Zhong, Xiang |
author_sort | Wu, Jiamin |
collection | PubMed |
description | Purpose: N (6)-methyladenosine (m(6)A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m(6)A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m(6)A RNA methylation in the liver of mice. Methods: A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m(6)A modification in the liver were assessed. Results: Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD. The amounts of serum low-density lipoprotein cholesterol (LDL), liver total cholesterol (TC), and triacylglycerol (TAG) were significantly decreased by resveratrol supplementation. In addition, resveratrol significantly enhanced the levels of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), cytochrome P450, family 4, subfamily a, polypeptide 10/14 (CYP4A10/14), acyl-CoA oxidase 1 (ACOX1), and fatty acid-binding protein 4 (FABP4) mRNA and inhibited acyl-CoA carboxylase (ACC) mRNA levels in the liver. Furthermore, the resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m(6)A abundance in mice liver. Conclusion: The beneficial effect of resveratrol on lipid metabolism disorder under HFD may be due to decrease of m(6)A RNA methylation and increase of PPARα mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice. |
format | Online Article Text |
id | pubmed-7845411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78454112021-01-30 Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation Wu, Jiamin Li, Yi Yu, Jiayao Gan, Zhending Wei, Wenyao Wang, Chao Zhang, Lili Wang, Tian Zhong, Xiang Front Pharmacol Pharmacology Purpose: N (6)-methyladenosine (m(6)A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m(6)A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m(6)A RNA methylation in the liver of mice. Methods: A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m(6)A modification in the liver were assessed. Results: Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD. The amounts of serum low-density lipoprotein cholesterol (LDL), liver total cholesterol (TC), and triacylglycerol (TAG) were significantly decreased by resveratrol supplementation. In addition, resveratrol significantly enhanced the levels of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), cytochrome P450, family 4, subfamily a, polypeptide 10/14 (CYP4A10/14), acyl-CoA oxidase 1 (ACOX1), and fatty acid-binding protein 4 (FABP4) mRNA and inhibited acyl-CoA carboxylase (ACC) mRNA levels in the liver. Furthermore, the resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m(6)A abundance in mice liver. Conclusion: The beneficial effect of resveratrol on lipid metabolism disorder under HFD may be due to decrease of m(6)A RNA methylation and increase of PPARα mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice. Frontiers Media S.A. 2020-12-18 /pmc/articles/PMC7845411/ /pubmed/33519432 http://dx.doi.org/10.3389/fphar.2020.568006 Text en Copyright © 2020 Wu, Li, Yu, Gan, Wei, Wang, Zhang, Wang and Zhong http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Wu, Jiamin Li, Yi Yu, Jiayao Gan, Zhending Wei, Wenyao Wang, Chao Zhang, Lili Wang, Tian Zhong, Xiang Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation |
title | Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation |
title_full | Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation |
title_fullStr | Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation |
title_full_unstemmed | Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation |
title_short | Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation |
title_sort | resveratrol attenuates high-fat diet induced hepatic lipid homeostasis disorder and decreases m(6)a rna methylation |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845411/ https://www.ncbi.nlm.nih.gov/pubmed/33519432 http://dx.doi.org/10.3389/fphar.2020.568006 |
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