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

Wei Yang; Mingmao Yang; Yan Tian; Qianming Jiang; Juan J Loor; Jie Cao; Shuang Wang; Changhong Gao; Wenwen Fan; Bingbing Zhang; Chuang Xu

doi:10.3390/metabo12111071

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

Metabolites. 2022 Nov 5;12(11):1071. doi: 10.3390/metabo12111071.

Authors

Wei Yang¹, Mingmao Yang^{1

2}, Yan Tian¹, Qianming Jiang³, Juan J Loor³, Jie Cao⁴, Shuang Wang¹, Changhong Gao¹, Wenwen Fan¹, Bingbing Zhang⁵, Chuang Xu^{1

4}

Affiliations

¹ College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
² Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A & F University, Xianyang 712100, China.
³ Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
⁴ College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
⁵ College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.

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.

Keywords: fatty acid metabolism; myricetin; oxidative stress; primary calf hepatocytes.

Abstract

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