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Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids

Authors :
Wei Yang
Mingmao Yang
Yan Tian
Qianming Jiang
Juan J. Loor
Jie Cao
Shuang Wang
Changhong Gao
Wenwen Fan
Bingbing Zhang
Chuang Xu
Source :
Metabolites, Vol 12, Iss 11, p 1071 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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 H2O2, 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 H2O2, 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.

Details

Language :
English
ISSN :
22181989
Volume :
12
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.866c86f825a42aaa90e9d3ab4a57616
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo12111071