An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training

• Published in: European journal of nutrition Vol. 52; no. 5; pp. 1523 - 1532
• Main Authors: Côté, Isabelle, Ngo Sock, Emilienne Tudor, Lévy, Émile, Lavoie, Jean-Marc
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2013; Springer Nature B.V
• Subjects: Acyl Coenzyme A; Acyl Coenzyme A - metabolism; adverse effects; Animal subjects; Animals; Carrier Proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; Chemistry; Chemistry and Materials Science; cholesterol; Cholesterol - metabolism; Cholesterol 7-alpha-Hydroxylase; Cholesterol 7-alpha-Hydroxylase - genetics; Cholesterol 7-alpha-Hydroxylase - metabolism; Cholesterol, VLDL; Cholesterol, VLDL - metabolism; diet; Diet, Atherogenic; Diet, Atherogenic - adverse effects; education programs; etiology; exercise; fatty liver; Fatty Liver - etiology; Fatty Liver - pathology; Fatty Liver - therapy; Female; Gene Expression; gene targeting; genetics; intestines; Intestines - metabolism; lipogenesis; Lipogenesis - physiology; liver; Liver - metabolism; Liver X Receptors; messenger RNA; metabolism; Nutrition; Original Contribution; Orphan Nuclear Receptors; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - metabolism; pathology; Physical Conditioning, Animal; Physical Endurance; physiology; Rats; Rats, Sprague-Dawley; receptors; Receptors, Cytoplasmic and Nuclear; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; squalene; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; therapy; triacylglycerols; Triglycerides; Triglycerides - metabolism; very low density lipoprotein; Cholesterol transport; Bile acid synthesis; Exercise; Liver cholesterol
• ISSN: 1436-6207; 1436-6215; 1436-6215
• DOI: 10.1007/s00394-012-0459-5

Purpose The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training. Methods Sprague–Dawley rats ( n  = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week. Results The AD resulted in a large ( P  < 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction ( P  < 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase ( P  < 0.001) in SREBP-1c and a decrease ( P  < 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts ( P  < 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding. Conclusions It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.