Phenotypic comparison of common mouse strains developing high-fat diet-induced hepatosteatosis
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- 作者：Melanie Kahle ; Marion Horsch ; Barbara Fridrich ; Anett Seelig ; J眉rgen Schulthei脽 ; J枚rn Leonhardt ; Martin Irmler ; Johannes Beckers ; Birgit Rathkolb ; Eckhard Wolf ; Nicole Franke ; Val茅rie Gailus-Durner ; Helmut Fuchs ; Martin Hrab臎 de Angelis ; Susanne Neschen
- 关键词：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
- 刊名：Molecular Metabolism
- 出版年：November, 2013
- 年：2013
- 卷：2
- 期：4
- 页码：435-446
- 全文大小：1326 K
文摘
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. 鈥淯niversal鈥?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.