Marchant, Nathan; Marchant Erik; Elison, Weston; Herring, Jacob; Yang, Haokun; Tessem, Jeffrey; Hancock, Chad (Brigham Young University)
Faculty Advisor: Hancock, Chad (Brigham Young University; Nutrition, Dietetics, and Food Science); Tessem, Jeffrey (Brigham Young University; Nutrition, Dietetics, and Food Science)
Purpose: To analyze the effect of the Nr4a3 gene on respiratory capacity of mitochondria in skeletal muscle of mice on a normal or high fat diet.
Methods: Nr4a3-/- and WT mice were fed a normal chow (NC) or high fat diet (HF) for at least 20 weeks. After euthanasia, soleus muscle was harvested and wet weight was measured and prepared for respirometry. Mitochondrial respiration was evaluated using an Oroboros Oxygraph Respirometer. Respiratory capacity comparisons were made with a two-way ANOVA and Tukey multiple comparison test.
Results: Oxygen consumption is reported as pmol/(s*mg wet tissue) and statistics are represented as mean ± SEM. In the WT male mice there was a decrease in coupled complex I supported respiration in HF vs. NC diet (25.9 ± 7.3 vs. 64.5 ± 5.0, p=0.004). In the HF WT group there was also a decrease in uncoupled respiration (61.4 ± 15.0 vs. 107.8 ± 7.1, p=0.0004) compared to NC WT. In female mice there was also a decrease between HF WT and NC WT in complex I (28.2 ± 3.7 vs. 57.4 ± 5.7, p=0.0005) and uncoupled respiration (87.1 ± 7.1 vs. 119.4 ± 8.9, p=0.0001). However, there was no significant difference between the WT NC mice and either of the Nr4a3-/- groups. Coupled complex I and uncoupled respiration states in both Nr4a3-/- groups were not significantly different from WT.
Conclusion: Feeding mice a high fat diet impairs proper mitochondrial function in muscle when compared to a normal chow diet. The decrease in respiration from the HF diet is dependent upon the function of the Nr4a3 gene, as no decrease was observed in Nr4a3-/- mice.