Aims: Exercise is well-established to be beneficial for obesity and T2D. This is in part, due to the regulation of hypoxia inducible factors (HIFs). We have created a novel mouse model which targets the beneficial effects of HIF in metabolism (HIF1α-N813Q). We aim to explore the effects of exercise and high fat diet (HFD) feeding in our novel HIF1α mouse model and hypothesise that mice with this mutation will experience some protection against adverse consequences of HFD, and experience greater benefits when given access to exercise.
Methods: Male HIF1α-N813Q mutant mice and their wild-type (WT) littermates underwent a series of basal tests for assessment of metabolic status and muscle function: glucose tolerance test (GTT), fore-limb grip strength, insulin tolerance test (ITT) and endurance testing. Mice were then challenged with HFD (Diet 6B; 45% digestible energy from lipids) and given access to a running wheel (locked for controls).
Results: Baseline data from metabolic tests did not exhibit any differences between genotypes in glucose and insulin tolerance, and baseline endurance or grip strength. Body weight gain and fat mass were significantly reduced in mutant mice given access to a wheel but not the other groups (mutant and control sedentary, control with wheel). As expected, 4 weeks of HFD-feeding significantly worsened GTT response in all groups, except for N813Q-mutant exercise mice. N813Q-exercise mice had significantly enhanced grip strength (p<0.05) and significantly increased exercise endurance after only 2 weeks which further increased by 6 weeks. The increase was significantly greater than in control-exercise mice which only showed a smaller increase in endurance at 6 weeks.
Conclusions: Overall, the data show that our novel HIF1α mice experience enhanced improvements in both muscle functionality and metabolism. This suggests that targeting this pathway is a potential mechanism to substantially augment the beneficial effects of exercise.