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Mol Metab. 2013 Aug 3;2(4):435-46. doi: 10.1016/j.molmet.2013.07.009. eCollection 2013.

Phenotypic comparison of common mouse strains developing high-fat diet-induced hepatosteatosis.

Author information

1
Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg/Munich, Germany ; German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 85764 Neuherberg/Munich, Germany.

Abstract

Genetic predisposition and environmental factors contribute to an individual's susceptibility to develop hepatosteatosis. In a systematic, comparative survey we focused on genotype-dependent and -independent adaptations early in the pathogenesis of hepatosteatosis by characterizing C3HeB/FeJ, C57BL/6NTac, C57BL/6J, and 129P2/OlaHsd mice after 7, 14, or 21 days high-fat-diet exposure. Strain-specific metabolic responses during diet challenge and liver transcript signatures in mild hepatosteatosis outline the suitability of particular strains for investigating the relationship between hepatocellular lipid content and inflammation, glucose homeostasis, insulin action, or organelle physiology. Genetic background-independent transcriptional adaptations in liver paralleling hepatosteatosis suggest an early increase in the organ's vulnerability to oxidative stress damage what could advance hepatosteatosis to steatohepatitis. "Universal" adaptations in transcript signatures and transcription factor regulation in liver link insulin resistance, type 2 diabetes mellitus, cancer, and thyroid hormone metabolism with hepatosteatosis, hence, facilitating the search for novel molecular mechanisms potentially implicated in the pathogenesis of human non-alcoholic-fatty-liver-disease.

KEYWORDS:

129, 129P2/OlaHsd; ALT, alanine aminotransferase; B6J, C57BL/6J; B6N, C57BL/6NTac; C3H, C3HeB/FeJ; Cancer; HDL, high-density lipoprotein; HFD, high-fat diet; IR, insulin resistance; Inflammation; Insulin resistance; LDL, low-density lipoprotein; LFD, low fat rodent laboratory diet; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic hepatosteatitis; Non-alcoholic fatty liver disease; Oxidative stress; T2D, type 2 diabetes mellitus; TAG, triacylglycerol; Thyroid metabolism; VLDL, very low density lipoprotein; WAT, white adipose tissue

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