Background: The orexigenic effect of NPY released from the arcuate nucleus (ARC) of the hypothalamus is well established. Chemogenetic activation of NPY neurons in either the ARC or the central nucleus of the amygdala (CeA) increases consumption of chow in fed-state animals. However, the role of NPY neurons on other feeding behaviors, such as macronutrient preference, in the ARC and CeA remains unclear. The current study aimed to investigate the role of NPY neurons on macronutrient (fat vs carbohydrate) preference in these two brain regions.
Methods: 8-12 week old NPYCre/+ C57BL/6 mice were bilaterally stereotaxically infused with an adeno-associated viral vector (AAV) expressing the excitatory (Gq) DREADD (AAV9-hM3Dq-mcherry) or control virus (AAV9-mcherry; 200nL/hemisphere). After 4 weeks of viral incubation, mice were intraperitoneally administered the DREADD agonist clozapine-N-oxide (CNO) or vehicle (saline) in a counterbalanced design. Animals were tested for both food consumption and macronutrient preference in a BioDAQ system for automated monitoring and recording of consumption.
Results: Chemogenetic activation of NPY neurons in both the ARC and the CeA increased consumption of chow, due to increases in both length and number of feeding bouts. Similarly, total consumption of intralipid and sucrose solutions were greater in Gq DREADD CNO-treated animals compared with control animals. Animals expressing the Gq DREADD within the ARC displayed a macronutrient preference for fat over carbohydrate following CNO treatment, however, there was no difference observed in fat vs carbohydrate preference during chemogenetic activation of NPY neurons in the CeA.
Conclusion: These results demonstrate the important role of neuropeptide Y neurons in both the ARC and the CeA for the regulation of food intake. However, our data suggest that only ARC, but not CeA, NPY neurons are involved in macronutrient preference as activation of CeA NPY neurons has no impact on preference between fat and carbohydrate.