Elsevier

Molecular Metabolism

Volume 2, Issue 4, November 2013, Pages 435-446
Molecular Metabolism

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

https://doi.org/10.1016/j.molmet.2013.07.009Get rights and content
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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.

Abbreviations

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

Keywords

Non-alcoholic fatty liver disease
Inflammation
Oxidative stress
Thyroid metabolism
Insulin resistance
Cancer

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