Exercise increases NPY/AgRP and TH neuron activity in the hypothalamus of female mice.

Recent evidence identifies a potent role for aerobic exercise to modulate the activity of hypothalamic neurons related to appetite; however, these studies have been primarily performed in male rodents. Since females have markedly different neuronal mechanisms regulating food intake, the current study aimed to determine the effects of acute treadmill exercise on hypothalamic neuron populations involved in regulating appetite in female mice. Mature, untrained female mice were exposed to acute sedentary, low- (10 m/min), moderate- (14 m/min), and high (18 m/min)-intensity treadmill exercise in a randomized crossover design. Mice were fasted 10 h before exercise, and food intake was monitored for 48 h after bouts. Immunohistochemical detection of cFOS was performed 3 h post-exercise to determine the changes in hypothalamic neuropeptide Y (NPY)/agouti-related peptide (AgRP), pro-opiomelanocortin (POMC), tyrosine hydroxylase (TH), and SIM1-expressing neuron activity concurrent with the changes in food intake. Additionally, stains for pSTAT3tyr705 and pERKthr202/tyr204 were performed to detect exercise-mediated changes in intracellular signaling. Briefly, moderate- and high-intensity exercises increased 24-h food intake by 5.9 and 19%, respectively, while low-intensity exercise had no effects. Furthermore, increases in NPY/AgRPARC, SIM1PVN, and TH neuron activity were observed 3 h after high-intensity exercise, with no effects on POMCARC neurons. While no effects of exercise on pERKthr202/tyr204 were observed, pSTAT3tyr705 was elevated specifically in NPY/AgRP neurons 3 h post-exercise. Overall, aerobic exercise increased the activity of several appetite-stimulating neuron populations in the hypothalamus of female mice, which may provide insight into previously reported sexual dimorphisms in post-exercise feeding.

Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice.

Emerging evidence identifies a potent role for aerobic exercise to modulate activity of neurons involved in regulating appetite; however, these studies produce conflicting results. These discrepancies may be, in part, due to methodological differences, including differences in exercise intensity and pre-exercise energy status. Consequently, the current study utilized a translational, well-controlled, within-subject, treadmill exercise protocol to investigate the differential effects of energy status and exercise intensity on post-exercise feeding behavior and appetite-controlling neurons in the hypothalamus. Mature, untrained male mice were exposed to acute sedentary, low (10m/min), moderate (14m/min), and high (18m/min) intensity treadmill exercise in a randomized crossover design. Fed and 10-hour-fasted mice were used, and food intake was monitored 48h. post-exercise. Immunohistochemical detection of cFOS was performed 1-hour post-exercise to determine changes in hypothalamic NPY/AgRP, POMC, tyrosine hydroxylase, and SIM1-expressing neuron activity concurrent with changes in food intake. Additionally, stains for pSTAT3tyr705 and pERKthr202/tyr204 were performed to detect exercise-mediated changes in intracellular signaling. Results demonstrated that fasted high intensity exercise suppressed food intake compared to sedentary trials, which was concurrent with increased anorexigenic POMC neuron activity. Conversely, fed mice experienced augmented post-exercise food intake, with no effects on POMC neuron activity. Regardless of pre-exercise energy status, tyrosine hydroxylase and SIM1 neuron activity in the paraventricular nucleus was elevated, as well as NPY/AgRP neuron activity in the arcuate nucleus. Notably, these neuronal changes were independent from changes in pSTAT3tyr705 and pERKthr202/tyr204 signaling. Overall, these results suggest fasted high intensity exercise may be beneficial for suppressing food intake, possibly due to hypothalamic POMC neuron excitation. Furthermore, this study identifies a novel role for pre-exercise energy status to differentially modify post-exercise feeding behavior and hypothalamic neuron activity, which may explain the inconsistent results from studies investigating exercise as a weight loss intervention.