Exercise Counters the Changes in Nutrient Sensing Gene Expression after Caloric Restriction and the Loss of Ovarian Function in Obesity‐prone Rats
Authors: Song Zhilin , Houck Julie A , Sherk Vanessa , Foright Rebecca , Presby David , Giles Erin , Jackman Matthew , MacLean Paul S 
Published: November 2023

BackgroundExercise counters the biological drive to regain weight after weight loss, both by reducing the drive to overfeed and by increasing expended energy beyond the cost of the exercise bout. We have hypothesized that exercise alters the nutrient sensing systems in the brain after weight reduction in a manner that would attenuate the drive to overfeed. In the present study, we examined the effect of exercise in female rats after the loss of ovarian function, when the drive to gain weight is known to be exacerbated. We specifically evaluated the gene expression of neural factors involved in glucose sensing and in the regulation of energy balance in the arcuate nucleus (ARC), ventral medial nucleus (VMN), supraoptic nucleus (SON) and amygdala (AMG).MethodDiet induced obese female rats were weight reduced (15% body weight) by restricting caloric intake, with (EX) or without (SED) a daily bout of treadmill exercise (60min/day, 6days/week, 15m/min). The rats were then surgically ovariectomized (OVX), and then allowed ad libitum access for 6 weeks. Food intake, weight gain, and body composition were monitored during this weight gain period. Ad libitum ovariectomized (AL) and sham‐operated (SHAM) rats were included in the design as controls. At the time of sacrifice, punch biopsies of ARC, VMN, SON and AMG were obtained and assayed for gene expression (mRNA) by qPCR. Outcomes included mRNA levels of glucokinase (GK), a hallmark of glucose sensing neurons, glucose transporter 2 and 3 (GLUT2, GLUT3), insulin receptor (InsR), oxytocin (OT), OT receptor (OTR), leptin receptor (LepR), and pro‐opiomelanocortin (POMC), a precursor polypeptide involved in appetite and metabolic regulation.ResultsIn the SON, both GLUT3 and InsR mRNAs were significantly lower in AL and SED rats compared to that in SHAM rats (approximately 40% and 60% lower, respectively), but these levels were restored in EX rats. In the AMG, exercise significantly increased OTR gene expression (about two fold). In the VMN, GK and GLUT3 gene expression decreased by approximately 25% and 30%, respectively in AL rats, and these further decreased in SED rats (~ 50% and 45% reduction, respectively), compared to that in SHAM rats. In both cases, regular exercise tended to restore these levels to that found in the SHAM rats. There was no significant change of GK, GLUT3, Glut2 or POMC mRNA in ARC.ConclusionThe loss of ovarian function altered the expression of critical factors involved in glucose sensing in the SON and VMN in a manner consistent with OVX‐induced overfeeding. Weight reduction through calorie restriction exacerbated some of these effects. Regular exercise, however, countered these combined effects on nutrient sensing gene expression in the SON, VMN, and AMG, and may elicit appetite suppressing effects by enhancing the capacity for and response to nutrients in circulation.Support or Funding InformationNIH P50 HD073063, NIH R01 CA164166, NIH P30 DK48520.