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Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids
Triacylglycerol (TAG) accumulation and oxidative damage in hepatocytes induced by high circulating concentrations of fatty acids (FA) are common after calving. In order to clarify the role of myricetin on lipid metabolism in hepatocytes when FA metabolism increases markedly, we performed in vitro an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698477/ https://www.ncbi.nlm.nih.gov/pubmed/36355155 http://dx.doi.org/10.3390/metabo12111071 |
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author | Yang, Wei Yang, Mingmao Tian, Yan Jiang, Qianming Loor, Juan J. Cao, Jie Wang, Shuang Gao, Changhong Fan, Wenwen Zhang, Bingbing Xu, Chuang |
author_facet | Yang, Wei Yang, Mingmao Tian, Yan Jiang, Qianming Loor, Juan J. Cao, Jie Wang, Shuang Gao, Changhong Fan, Wenwen Zhang, Bingbing Xu, Chuang |
author_sort | Yang, Wei |
collection | PubMed |
description | Triacylglycerol (TAG) accumulation and oxidative damage in hepatocytes induced by high circulating concentrations of fatty acids (FA) are common after calving. In order to clarify the role of myricetin on lipid metabolism in hepatocytes when FA metabolism increases markedly, we performed in vitro analyses using isolated primary calf hepatocytes from three healthy female calves (1 d old, 42 to 48 kg). Two hours prior to an FA challenge (1.2 mM mix), the hepatocytes were treated with 100 μM (M1), 50 μM (M2), or 25 μM (M3) of myricetin. Subsequently, hepatocytes from each donor were challenged with or without FA for 12 h in an attempt to induce metabolic stress. Data from calf hepatocyte treatment comparisons were assessed using two-way repeated-measures (RM) ANOVA with subsequent Bonferroni correction. The data revealed that hepatocytes challenged with FA had greater concentrations of TAG and nonesterified fatty acids (NEFA), oxidative stress-related MDA and H(2)O(2), and mRNA and protein abundance of lipid synthesis-related SREBF1 and inflammatory-related NF-κB. In addition, the mRNA abundance of the lipid synthesis-related genes FASN, DGAT1, DGAT2, and ACC1; endoplasmic reticulum stress-related GRP79 and PERK; and inflammatory-related TNF-α also were upregulated. In contrast, the activity of antioxidant SOD (p < 0.01) and concentrations of GSH (p < 0.05), and the protein abundance of mitochondrial FA oxidation-related CPT1A, were markedly lower. Compared with FA challenge, 50 and 100 μM myricetin led to lower concentrations of TAG, NEFA, MDA, and H(2)O(2), as well as mRNA and protein abundance of SREBF1, DGAT1, GRP78, and NF-κB. In contrast, the activity of SOD (p < 0.01) and mRNA and protein abundance of CPT1A were markedly greater. Overall, the results suggest that myricetin could enhance the antioxidant capacity and reduce lipotoxicity, endoplasmic reticulum stress, and inflammation. All of these effects can help reduce TAG accumulation in hepatocytes. |
format | Online Article Text |
id | pubmed-9698477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96984772022-11-26 Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids Yang, Wei Yang, Mingmao Tian, Yan Jiang, Qianming Loor, Juan J. Cao, Jie Wang, Shuang Gao, Changhong Fan, Wenwen Zhang, Bingbing Xu, Chuang Metabolites Article Triacylglycerol (TAG) accumulation and oxidative damage in hepatocytes induced by high circulating concentrations of fatty acids (FA) are common after calving. In order to clarify the role of myricetin on lipid metabolism in hepatocytes when FA metabolism increases markedly, we performed in vitro analyses using isolated primary calf hepatocytes from three healthy female calves (1 d old, 42 to 48 kg). Two hours prior to an FA challenge (1.2 mM mix), the hepatocytes were treated with 100 μM (M1), 50 μM (M2), or 25 μM (M3) of myricetin. Subsequently, hepatocytes from each donor were challenged with or without FA for 12 h in an attempt to induce metabolic stress. Data from calf hepatocyte treatment comparisons were assessed using two-way repeated-measures (RM) ANOVA with subsequent Bonferroni correction. The data revealed that hepatocytes challenged with FA had greater concentrations of TAG and nonesterified fatty acids (NEFA), oxidative stress-related MDA and H(2)O(2), and mRNA and protein abundance of lipid synthesis-related SREBF1 and inflammatory-related NF-κB. In addition, the mRNA abundance of the lipid synthesis-related genes FASN, DGAT1, DGAT2, and ACC1; endoplasmic reticulum stress-related GRP79 and PERK; and inflammatory-related TNF-α also were upregulated. In contrast, the activity of antioxidant SOD (p < 0.01) and concentrations of GSH (p < 0.05), and the protein abundance of mitochondrial FA oxidation-related CPT1A, were markedly lower. Compared with FA challenge, 50 and 100 μM myricetin led to lower concentrations of TAG, NEFA, MDA, and H(2)O(2), as well as mRNA and protein abundance of SREBF1, DGAT1, GRP78, and NF-κB. In contrast, the activity of SOD (p < 0.01) and mRNA and protein abundance of CPT1A were markedly greater. Overall, the results suggest that myricetin could enhance the antioxidant capacity and reduce lipotoxicity, endoplasmic reticulum stress, and inflammation. All of these effects can help reduce TAG accumulation in hepatocytes. MDPI 2022-11-05 /pmc/articles/PMC9698477/ /pubmed/36355155 http://dx.doi.org/10.3390/metabo12111071 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Wei Yang, Mingmao Tian, Yan Jiang, Qianming Loor, Juan J. Cao, Jie Wang, Shuang Gao, Changhong Fan, Wenwen Zhang, Bingbing Xu, Chuang Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids |
title | Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids |
title_full | Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids |
title_fullStr | Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids |
title_full_unstemmed | Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids |
title_short | Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids |
title_sort | effect of myricetin on lipid metabolism in primary calf hepatocytes challenged with long-chain fatty acids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698477/ https://www.ncbi.nlm.nih.gov/pubmed/36355155 http://dx.doi.org/10.3390/metabo12111071 |
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