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Am J Physiol Gastrointest Liver Physiol 297: G378-G384, 2009. First published June 18, 2009; doi:10.1152/ajpgi.90543.2008
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LIVER AND BILIARY TRACT

Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet

Sean W. P. Koppe,1 Marc Elias,1 Richard H. Moseley,2 and Richard M. Green1

1Division of Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and 2Medical Service, Ann Arbor Veterans Affairs Healthcare System, Division of Gastroenterology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan

Submitted 11 September 2008 ; accepted in final form 10 June 2009

Diets high in trans fats are associated with an increased risk of cardiovascular disease and components of the metabolic syndrome. The influence of these toxic fatty acids on the development of nonalcoholic fatty liver disease has not been significantly examined. Therefore, we sought to compare the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats. Male AKR/J mice were fed a calorically identical trans fat diet or standard high-fat diet for 10 days, 4 wk, and 8 wk. Serum alanine aminotransferase (ALT), lipid, insulin, and leptin levels were determined and the quantitative insulin-sensitivity check index (QUICKI) was calculated as a measure of insulin resistance. Additionally, hepatic triglyceride content and gene expression of several proinflammatory genes were assessed. By 8 wk, trans fat-fed mice exhibited higher ALT values than standard high-fat-fed mice (126 ± 16 vs. 71 ± 7 U/l, P < 0.02) despite similar hepatic triglyceride content at each time point. Trans fat-fed mice also had increased insulin resistance compared with high-fat-fed mice at 4 and 8 wk with significantly higher insulin levels and lower QUICKI values. Additionally, hepatic interleukin-1β (IL-1β) gene expression was 3.6-fold higher at 4 wk (P < 0.05) and 5-fold higher at 8 wk (P < 0.05) in trans fat-fed mice compared with standard high-fat-fed mice. Trans fat feeding results in higher ALT values, increased insulin resistance, and elevated IL-1β levels compared with standard high-fat feeding.

elaidic acid; nonalcoholic fatty liver disease, interleukin-1β; quantitative insulin-sensitivity check index, trans fat



Address for reprint requests and other correspondence: S. W. P. Koppe, Division of Hepatology, Searle 10-567, 300 E. Chicago, Chicago, IL 60611 (e-mail: s-koppe{at}northwestern.edu, m-elias{at}northwestern.edu, rmoseley{at}umich.edu, r-green2{at}northwestern.edu)







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