High Fat Fed Nr4a1 Knock Out Mouse has Significant Modulation of Mitochondrial Respiration Across Various Tissues

Abstract

The orphan nuclear receptor Nr4a1 is critical for fuel utilization in various tissues. Studies have shown that Nr4a1 controls expression of genes necessary for mitochondrial respiration. Further studies have demonstrated that Nr4a1 knock out animals fed a high fat diet have significant shifts in fuel utilization profiles. We sought to define the changes in mitochondrial respiration and function across various tissues in wild type and Nr4a1 KO mice fed a normal chow or high fat chow diet for twenty weeks. Nr4a1 KO mice fed the high fat diet had significantly worse glucose tolerance than wild type animals fed the high fat diet. Furthermore, Nr4a1 deficient animals demonstrated significant changes in the macrophage population as compared to wild type animals. Mitochondrial respiration of muscle and liver from Nr4a1 KO animals fed normal chow or high fat diet were significantly impaired compared to the wild type controls. Interestingly, mitochondrial respiration from macrophages was significantly enhanced in the Nr4a1 KO animals. These data demonstrate systemic effects of Nr4a1 deletion, as well as demonstrating a mechanism by which Nr4a1 KO have shifts in fuel utilization during high fat feeding regimes.Support or Funding InformationThis study was funded by a BYU ORCA Grant to KG and a BYU MEG Grant to JST.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.