Integration of hepatic lipidomics and transcriptomics reveals the effect of butter-derived ruminant trans fatty acids on lipid metabolism in C57BL/6J mice

Abstract

Dysregulation of lipid metabolism results in metabolism-related diseases. Our previous research indicated that 1.3% E and 4% E ruminant trans fatty acids (R-TFA) caused dyslipidemia and promoted atherosclerotic plaques in ApoE^−/− mice, presenting detrimental effects. However, the effect of R-TFA on the lipid metabolism of normal mice remains unclear. Therefore, our current research aims to explore the effects of butter-derived R-TFAs on the lipid metabolism of C57BL/6J mice through the integration of lipidomics and transcriptomics. As a result, we found that 1.3% E butter-derived R-TFA promoted dyslipidemia and impaired hepatic function in C57BL/6J mice fed a high-fat diet, which was associated with an increase in DG (18:1/22:5), TG (18:1/18:2/22:4) and FA (24:5) as determined through lipidomics analysis, but had a less significant effect on C57BL/6J mice fed a low-fat diet. Through a combination analysis and verification of gene expression, we found that the arachidonic acid pathway might be involved in the disruption of lipid metabolism by butter-derived R-TFA. In addition, butter-derived R-TFA up-regulated the expression of unigene thromboxane-A synthase 1 (Tbxas1), arachidonate lipoxygenase 3 (Aloxe3), acyl-coenzyme A thioesterase 2 (Acot2), epoxide hydrolase 2 (Ephx2) and carbonyl reductase 3 (Cbr3) in C57BL/6J mice fed a high-fat diet. Herein, our research provides a new perspective for exploring the effects of butter-derived R-TFA on lipid metabolism and speculates on the possible mechanism of lipid metabolism disorder induced by butter-derived R-TFA in C57BL/6J mice fed a high-fat diet.