NMDA Receptors in POMC Neurons Connect Exercise With Insulin Sensitivity.

Autor: Portillo, Bryan, Hwang, Eunsang, Ajwani, Jason, Grose, Kyle, Lieu, Linh, Wallace, Briana, Kabahizi, Anita, Elmquist, Joel K., Williams, Kevin W.
Předmět:
Zdroj: Diabetes; 12/1/2024, Vol. 73 Issue 12, p1942-1951, 10p
Abstrakt: Increased arcuate proopiomelanocortin (POMC) neuron activity improves glucose metabolism and reduces appetite, facilitating weight loss. We recently showed that arcuate POMC neurons are activated by exercise. However, the role of excitatory glutamatergic input in these neurons and the metabolic outcomes of exercise remains undefined. To investigate this, we developed a mouse model with NMDA receptors (NMDARs) selectively deleted from POMC neurons of adult mice. We performed metabolic assessments, including the monitoring of body weight, body composition analysis, and glucometabolic tolerance tests. We also examined the metabolic outcomes of these mice in response to exercise, including changes in arcuate POMC neuronal activity and insulin sensitivity. Loss of NMDARs in POMC neurons failed to alter body weight or body composition. Notably, however, we did observe a marked impairment in glucose tolerance and insulin sensitivity. Additionally, exercise resulted in activation of arcuate POMC neurons and a sustained improvement in insulin sensitivity, an effect that was abrogated in mice deficient for NMDARs in POMC neurons when compared with their respective sedentary controls. This underscores an important link among exercise, hypothalamic neuron function, and metabolic health. Moreover, this highlights an underappreciated role of hypothalamic POMC neurons in mediating beneficial effects of exercise on glucose metabolism. Article Highlights: High-intensity interval exercise (HIIE) causes a sustained improvement in insulin sensitivity. Melanocortin neurons are required for increasing insulin sensitivity following HIIE. NMDA receptors in POMC neurons are necessary for improved insulin sensitivity after HIIE. Activation of arcuate POMC neurons following HIIE relies on NMDA receptors. 6361200013112 dbi240002video1 Video 1. Video 1. American Diabetes Association 84th Scientific Sessions: Diabetes Journal Symposium—It Is All in Your Head—Central Nervous System Control of Systemic Metabolism. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index