Role of glucocorticoid signaling in exercise-associated changes in high-fat diet preference in rats

Abstract

The simultaneous introduction of wheel running (WR) and diet choice (high-carbohydrate chow vs. high-fat diet) results in sex-specific diet choice patterns in rats. WR induces a high-fat (HF) diet avoidance, and such avoidance persists in the majority of males, but not females, throughout a 2-wk period. Exercise is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates glucocorticoid (GC) release, which can alter dietary preferences. Here, we examined the role of the HPA axis and GC signaling in mediating exercise-induced changes in diet preference and the associated neurobiological adaptations that may underlie sex differences in diet choice patterns. Experiment 1 revealed that adrenalectomy did not significantly alter the initiation and persistence of running-induced HF diet avoidance in male rats. Experiment 2 showed that acute WR resulted in greater neural activation than chronic WR in the medial prefrontal (mPFC) and insular cortices (IC) in male rats. Experiment 3 revealed sex differences in the molecular adaptation to exercise and diet preference. First, exercise increased gene expression of fkbp5 in the mPFC, IC, and hippocampus of WR females but had limited influence in males. Second, male and female WR rats that reversed or maintained HF diet avoidance showed distinct sex- and HF diet preference-dependent expression profiles of genes involved in cortical GC signaling (e.g., nr3c1, nr3c2, and src1). Taken together, our results suggest sex differences in region-specific neural adaptations may underlie sex differences in diet preference and the health benefits from exercise.

Sex-Dependent Wheel Running Effects on High Fat Diet Preference, Metabolic Outcomes, and Performance on the Barnes Maze in Rats

“…While this crossover effect is influenced by exercise duration and intensity, it may partially contribute to differences in macronutrient preference among sedentary and physically active individuals. Our previous short-term studies with the same paradigm of wheel running and two-diet choice revealed that the majority of male rats express persistent HF diet avoidance whereas the majority of females reverse HF diet avoidance [80,[93][94][95]. These results are consistent with the report that estradiol enhances lipid metabolism during exercise in rats [96].…”

Chronic running‐wheel exercise from adolescence leads to increased anxiety and depression‐like phenotypes in adulthood in rats: Effects on stress markers and interaction with BDNF Val66Met genotype

“…Further studies have shown that chronic mild stress in rats leads to increased gene expression of GR and Sgk1 in the prefrontal cortex but not hippocampus, while Fkbp5 was increased in both regions (Wei et al., 2016). An 18‐day voluntary wheel running protocol has also been shown to increase Fkbp5 expression in the medial prefrontal cortex and hippocampus of female but not male rats (Yang et al., 2020). From the gene expression analysis, it is therefore unclear if the changes we have seen in our exercise rats indicate a level of stress or not.…”

Building Resilience with Aerobic Exercise: Role of FKBP5

“…A recent study has found an increase in the gene expression of FKBP5 in relevant limbic areas (e.g. mPFC, insular cortex and hippocampus) after a protocol of wheel-running [29,30]. It is possible that the enhancement of FKBP5 after running is induced by glucocorticoids (GCs) increase owing to the stressful, but positive, nature of aerobic exercise.…”