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

作者：Kahle Melanie; Horsch Marion; Fridrich Barbara; Seelig Anett; Schultheiss Juergen; Leonhardt Joern; Irmler Martin; Beckers Johannes; Rathkolb Birgit; Wolf Eckhard; Franke Nicole; Gailus Durner Valerie; Fuchs Helmut; de Angelis Martin Hrabe; Neschen Susanne^*

来源：Molecular Metabolism, 2013, 2(4): 435-446.

DOI：10.1016/j.molmet.2013.07.009

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

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.

• 出版日期2013-11