Intake of trans Fatty Acids Causes Nonalcoholic Steatohepatitis and Reduces Adipose Tissue Fat Content

• Published in: The Journal of nutrition Vol. 140; no. 6; pp. 1127 - 1132
• Main Authors: Machado, Roberta M, Stefano, José T, Oliveira, Claudia P.M.S, Mello, Evandro S, Ferreira, Fabiana D, Nunes, Valeria S, de Lima, Vicência M.R, Quintão, Eder C.R, Catanozi, Sergio, Nakandakare, Edna R, Lottenberg, Ana Maria P
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.06.2010
• Subjects: adipose tissue; Adipose Tissue - drug effects; animal models; Animals; Biological and medical sciences; biomarkers; blood; Blood Glucose; Blood Glucose - drug effects; chemically induced; Dietary Fats; Dietary Fats - pharmacology; drug effects; Fatty Acids; Fatty Acids - toxicity; Fatty Acids, Unsaturated; Fatty Acids, Unsaturated - toxicity; fatty liver; Fatty Liver - chemically induced; Feeding. Feeding behavior; food intake; Fundamental and applied biological sciences. Psychology; genetics; Insulin; Insulin - blood; lipid content; lipogenesis; Lipoproteins; Male; Metabolic Syndrome; metabolism; Mice; Mice, Knockout; nonalcoholic steatohepatitis; pharmacology; polyunsaturated fatty acids; Receptors, LDL; Receptors, LDL - genetics; Receptors, LDL - metabolism; toxicity; trans fatty acids; Trans Fatty Acids - toxicity; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Adipose tissue; Trans fatty acid; Nutrition; Trans stereoisomer; Lipids; Fat content; Fatty acids
• ISSN: 0022-3166; 1541-6100; 1541-6100
• DOI: 10.3945/jn.109.117937

We investigated the effects of dietary trans fatty acids, PUFA, and SFA on body and liver fat content, liver histology, and mRNA of enzymes involved in fatty acid metabolism. LDL receptor knockout weaning male mice were fed for 16 wk with diets containing 40% energy as either trans fatty acids (TRANS), PUFA, or SFA. Afterwards, subcutaneous and epididymal fat were weighed and histological markers of nonalcoholic fatty liver disease (NAFLD) were assessed according to the Histological Scoring System for NAFLD. PPARα, PPARγ, microsomal triglyceride transfer protein (MTP), carnitine palmitoyl transferase 1 (CPT-1), and sterol regulatory element binding protein-1c (SREBP-1c) mRNA were measured by quantitative RT-PCR. Food intake was similar in the 3 groups, although mice fed the TRANS diet gained less weight than those receiving the PUFA diet. Compared with the PUFA- and SFA-fed mice, TRANS-fed mice had greater plasma total cholesterol (TC) and triglyceride (TG) concentrations, less epididymal and subcutaneous fat, larger livers with nonalcoholic steatohepatitis (NASH)-like lesions, and greater liver TC and TG concentrations. Macrosteatosis in TRANS-fed mice was associated with a higher homeostasis model assessment of insulin resistance (HOMAIR) index and upregulated mRNA related to hepatic fatty acid synthesis (SREBP-1c and PPARγ) and to downregulated MTP mRNA. Diet consumption did not alter hepatic mRNA related to fatty acid oxidation (PPARα and CPT-1). In conclusion, compared with PUFA- and SFA-fed mice, TRANS-fed mice had less adiposity, impaired glucose tolerance characterized by greater HOMAIR index, and NASH-like lesions due to greater hepatic lipogenesis. These results demonstrate the role of trans fatty acid intake on the development of key features of metabolic syndrome.