Wheel running leads to sex-specific effects on Western diet-associated glucose homeostasis and brain insulin signaling without altering food-related impulsive choice

ABSTRACT

Objectives

There is a clear association between obesity and impulsivity. While exercise can suppress weight gain and decrease impulsive choice (IC), the relationship between impulsivity, the consumption of palatable, energy dense diets, and exercise is unclear. We examined IC before and after Western diet (WD) exposure in rats of both sexes and whether exercise would rescue any diet-mediated increases in IC. Our hypotheses were twofold: first, increased impulsivity would be associated with higher WD preference in a positive feedback loop and second, increased WD consumption would impair both peripheral and central insulin signaling, both of which exercise would attenuate.

Methods

Following baseline assessment of IC through a delay discounting task, rats were divided into naïve, sedentary (Sed), or wheel running (WR) groups for a 5-week WR and two-diet choice period after which rats underwent an oral glucose (OGTT) and insulin tolerance test (ITT) in addition to a re-test of IC. Insulin induced Akt-GSK3β signaling in the brain was examined using western blot.

Results

All Sed rats preferred the WD diet, and all WR rats initially avoided the WD but subsequently reversed their avoidance to preference with females reversing earlier than males. Exercise suppressed weight gain and adiposity to a greater extent in males than females. Only WR males showed improved glucose clearance during OGTT, but both male and female WR rats had a faster recovery of hypoglycemia during ITT. Furthermore, WR rescued WD-induced deficits in hypothalamic Akt-GSK3β signaling in males but not females. In the prefrontal cortex, however, WD and WR both reduced Akt-GSK3β signaling in males but not females. There were no sex differences in IC at baseline, and all rats made more impulsive choices during the re-test independent of diet, sex, or exercise.

Discussion

The results suggest that while exercise may have a greater efficacy at attenuating diet-mediated metabolic dysregulation in males, it has some beneficial effects for females and highlights the need to develop sex-specific interventions for restoring energy balance.

KEYWORDS:

• Wheel running
• Western diet
• impulsive choice
• oral glucose tolerance test
• insulin tolerance test
• insulin signaling
• sex differences

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgments

We thank Zijun Gao, Rashmi Ghonasgi, and David Tkac for their help with animal care.

Conflicts of interest

The authors declare no conflict of interest.

Ethics approval

All experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Illinois and in accordance with National Research Council’s Guide for the Care and Use of Laboratory Animals in the USA.

Additional information

Funding

This study was supported by the UIUC Psychology Department startup funds (to N-C.L.).