Hepatic Metabolic, Inflammatory, and Stress-Related Gene Expression in Growing Mice Consuming a Low Dose ofTrans-10,cis-12-Conjugated Linoleic Acid

Abstract

Dietarytrans-10,cis-12-conjugated linoleic acid (trans-10,cis-12-CLA) fed to obese and nonobese rodents reduces body fat but leads to greater liver mass due to steatosis. The molecular mechanisms accompanying such responses remain largely unknown. Our study investigated the effects of chronic lowtrans-10,cis-12-CLA supplementation on hepatic expression of 39 genes related to metabolism, inflammation, and stress in growing mice. Feeding a diet supplemented with 0.3%trans-10,cis-12-CLA (wt/wt basis) for 6 weeks increased liver mass and concentration of long-chain fatty acids (LCFAs) in liver, while adipose tissue mass decreased markedly. These changes were accompanied by greater expression of genes involved in LCFA uptake (Cd36), lipogenesis, and triacylglycerol synthesis (Acaca,Gpam,Scd,Pck1,Plin2). Expression of these genes was in line with upregulation of the lipogenic transcription factorSrebf1. Unlike previous studies where higher >0.50% of the diet) doses oftrans-10,cis-12-CLA were fed, we found greater expression of genes associated with VLDL assembly/secretion (Mttp,Cideb), ketogenesis (Hmgcs2,Bdh1), and LCFA oxidation (Acox1,Pdk4) in response totrans-10,cis-12-CLA. Dietary CLA, however, did not affect inflammation- and stress-related genes. Results suggested that a chronic low dose of dietary CLA increases liver mass and lipid accumulation due to activation of lipogenesis and insufficient induction of LCFA oxidation and VLDL assembly/secretion.