Ghrelin-Responsive Mediobasal Hypothalamic Neurons Mediate Exercise-Induced Food Intake and Endurance

• Published in: Obesity (Silver Spring, Md.) Md.), 2023-11, Vol.31, p.49-50
• Main Authors: Singh, Omprakash, Ogden, Sean, Varshney, Salil, Shankar, Kripa, Gupta, Deepali, Paul, Subhojit, Osborne-Lawrence, Sherri, Richard, Corine, Metzger, Nathan, Lawrence, Connor, Zigman, Jeffrey
• Format: Article
• Language: English
• Subjects: Food; Glucose
• ISSN: 1930-7381; 1930-739X

Background: The orexigenic hormone ghrelin doubles during high-intensity interval exercise (HIIE). Without the action of this increased ghrelin (as in mice that lack the ghrelin receptor, GHSR), exercise reduces food intake. Also, GHSR-null mice exhibit diminished endurance. These data suggest that ghrelin limits the capacity of exercise to restrict food intake but enhances exercise endurance. Here, we determined if GHSR-expressing neurons in the mediobasal hypothalamus (MBH) mediate effects of exercise on food intake and regulate exercise endurance. Methods: We stereotaxically delivered the inhibitory DREADD virus AAV2-hSyn-DIO-hM4(Gi)-mCherry to the MBH of Ghsr-IRES-Cre mice. CNO was administered to chemogenetically inhibit the activity of GHSR-expressing neurons infected with the inhibitory DREADD virus. We submitted these mice to HIIE and exercise endurance protocols, assessed food intake in response to administered ghrelin, and performed an oral glucose tolerance test. We used histochemistry to characterize mice as correctly-targeted ("hits," n = 16) or incorrectly-targeted ("misses," n = 11). Results: Inhibiting DREADD-infected, GHSR-expressing MBH neurons with CNO reduced food intake after HIIE (by 33.8%) and decreased running distance (by 20.7%), running duration (by 14.7%), and maximal speed (by 16.1%) during endurance exercise. It also increased blood glucose (by 18.4%) and lactate (by 24.6%) levels after endurance exercise and reduced administered ghrelin-induced food intake and c-fos by 42.6% and 28.8%, respectively. Glucose tolerance was unaffected. Conclusions: Activation of ghrelin-responsive MBH neurons is required for the normal feeding response to HIIE, the usual amount of endurance exhibited by mice during a forced exercise endurance protocol, food intake in response to administered ghrelin, and the usual blood glucose and lactate responses to prolonged exercise.