Hepatic Adaptations to a High Fat Diet in the MRL Mouse Strain are Associated with an Inefficient Oxidative Phosphorylation System.

The MRL mice are resistant to a 12-week high fat diet (HFD) feeding protocol, with the proximal cause being an increased basal pAMPKT172 expression in the skeletal muscle. Here, we test if this lack of pathology extends to the liver at both the tissue and cellular levels and its correlation to pAMPKT172 levels. MRL and B6 mice were subjected to 12 weeks of diet intervention and tissues were either fixed for histology or snap-frozen for further processing (n= 3-6, per group). The HFD MRL mice remain insulin and glucose sensitive after 12 weeks of HFD. This phenomenon is correlated to increased liver pAMPKT172. The HFD-fed B6 control strain demonstrates the opposite trend with decreased pAMPKT172 expression after the HFD period. We have found further evidence of differential MRL metabolic adaptations. These differences include reduced glycogen content, reduced ectopic fat storage, and increased expression of Complex II (CII) and Complex V of the Electron Transport Chain (ETC). Whereas, B6 HFD control show unchanged glycogen content, increased ectopic fat and increased expression of Complex I and Complex V of the ETC. Taken together, the MRL adaptations point to an inefficient energy-producing phenotype that leads to glycogen depletion and attenuation of ectopic fat as secondary consequences with AMPK as the signaling mediator of these HFD- hepatic adaptations.