title: Phenotypic comparison of common mouse strains developing high-fat diet-induced hepatosteatosis.
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.
authors: 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.
authors: Melanie
authors: M
authors: Kahle
authors: Marion
authors: M
authors: Horsch
authors: Barbara
authors: B
authors: Fridrich
authors: Anett
authors: A
authors: Seelig
authors: Jürgen
authors: J
authors: Schultheiß
authors: Jörn
authors: J
authors: Leonhardt
authors: Martin
authors: M
authors: Irmler
authors: Johannes
authors: J
authors: Beckers
authors: Birgit
authors: B
authors: Rathkolb
authors: Eckhard
authors: E
authors: Wolf
authors: Nicole
authors: N
authors: Franke
authors: Valérie
authors: V
authors: Gailus-Durner
authors: Helmut
authors: H
authors: Fuchs
authors: Martin Hrabě
authors: MH
authors: de Angelis
authors: Susanne
authors: S
authors: Neschen
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