Nearly two-thirds of U.S. adults are overweight or obese, putting them at risk for other serious medical conditions, including diabetes and heart disease. The medial amygdalar nucleus (MeA) regulates the intersection of stress, social behavior, and metabolism. We found that MeA neuronal activity is regulated by glucose. Using viral tracers, we mapped the projections of glucose-sensing neurons in the MeA and found they project to multiple downstream sites that are known to play a role in glucose metabolism. MeA neurons also form part of polysynaptic pathways to organs such as the pancreas, that are critical for glucose regulation. Chemogenetic activation of MeA neurons in both male and female mice alters home cage feeding, an effect that is most prominent when animals are in the fed state and presented with palatable food. This phenotype is not affected by administration of propranolol, a beta adrenergic receptor antagonist that can alleviate hypneophagia. Activation of the MeA does not alter anxiety-related behavior on the elevated plus maze, open field, or light-dark box. Optogenetic activation of MeA neurons expressing glucokinase, a putative marker of glucose-sensing neurons in the brain, mimics the feeding phenotype, suggesting that MeA suppression of feeding may be mediate through these neurons. Future work will delineate the role of specific MeA neural populations in glucose metabolism.
S. Stanley: Consultant; Self; Redpin Therapeutics. K. Devarakonda: None. A. Alvarsson: None. M. Bayne: None.
American Diabetes Association/Pathway to Stop Diabetes (1-17-ACE-31 to S.S.); National Institutes of Health (1R01NS097184, OT2OD024912); Alexandrine and Alexander L. Sinsheimer Fund