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Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent.

Abstract

The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fructose corn syrup (HFCS) equivalent for 1-16 wk were compared with mice fed standard chow or mice with trans fats or HFCS omitted. Cage racks were removed from western diet mice to promote sedentary behavior. By 16 wk, trans fat-fed mice became obese and developed severe hepatic steatosis with associated necroinflammatory changes. Plasma alanine aminotransferase levels increased, as did liver TNF-alpha and procollagen mRNA, indicating an inflammatory and profibrogenic response to injury. Glucose intolerance and impaired fasting glucose developed within 2 and 4 wk, respectively. Plasma insulin, resistin, and leptin levels increased in a profile similar to that seen in patients with NASH. The individual components of this diet contributed to the phenotype independently; isocaloric replacement of trans fats with lard established that trans fats played a major role in promoting hepatic steatosis and injury, whereas inclusion of HFCS promoted food consumption, obesity, and impaired insulin sensitivity. Combining risk factors for the metabolic syndrome by feeding mice trans fats and HFCS induced histological features of NASH in the context of a metabolic profile similar to patients with this disease. Because dietary trans fats promoted liver steatosis and injury, their role in the epidemic of NASH needs further evaluation.

Authors+Show Affiliations

Department of Internal Medicine, Saint Louis University, MO, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18772365

Citation

Tetri, Laura H., et al. "Severe NAFLD With Hepatic Necroinflammatory Changes in Mice Fed Trans Fats and a High-fructose Corn Syrup Equivalent." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 295, no. 5, 2008, pp. G987-95.
Tetri LH, Basaranoglu M, Brunt EM, et al. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol. 2008;295(5):G987-95.
Tetri, L. H., Basaranoglu, M., Brunt, E. M., Yerian, L. M., & Neuschwander-Tetri, B. A. (2008). Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. American Journal of Physiology. Gastrointestinal and Liver Physiology, 295(5), pp. G987-95. doi:10.1152/ajpgi.90272.2008.
Tetri LH, et al. Severe NAFLD With Hepatic Necroinflammatory Changes in Mice Fed Trans Fats and a High-fructose Corn Syrup Equivalent. Am J Physiol Gastrointest Liver Physiol. 2008;295(5):G987-95. PubMed PMID: 18772365.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. AU - Tetri,Laura H, AU - Basaranoglu,Metin, AU - Brunt,Elizabeth M, AU - Yerian,Lisa M, AU - Neuschwander-Tetri,Brent A, Y1 - 2008/09/04/ PY - 2008/9/6/pubmed PY - 2009/1/7/medline PY - 2008/9/6/entrez SP - G987 EP - 95 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 295 IS - 5 N2 - The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fructose corn syrup (HFCS) equivalent for 1-16 wk were compared with mice fed standard chow or mice with trans fats or HFCS omitted. Cage racks were removed from western diet mice to promote sedentary behavior. By 16 wk, trans fat-fed mice became obese and developed severe hepatic steatosis with associated necroinflammatory changes. Plasma alanine aminotransferase levels increased, as did liver TNF-alpha and procollagen mRNA, indicating an inflammatory and profibrogenic response to injury. Glucose intolerance and impaired fasting glucose developed within 2 and 4 wk, respectively. Plasma insulin, resistin, and leptin levels increased in a profile similar to that seen in patients with NASH. The individual components of this diet contributed to the phenotype independently; isocaloric replacement of trans fats with lard established that trans fats played a major role in promoting hepatic steatosis and injury, whereas inclusion of HFCS promoted food consumption, obesity, and impaired insulin sensitivity. Combining risk factors for the metabolic syndrome by feeding mice trans fats and HFCS induced histological features of NASH in the context of a metabolic profile similar to patients with this disease. Because dietary trans fats promoted liver steatosis and injury, their role in the epidemic of NASH needs further evaluation. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/18772365/Severe_NAFLD_with_hepatic_necroinflammatory_changes_in_mice_fed_trans_fats_and_a_high_fructose_corn_syrup_equivalent_ L2 - http://www.physiology.org/doi/full/10.1152/ajpgi.90272.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -