Long Chain Fatty Acids Differentially Regulate Sub-populations of Arcuate POMC and NPY Neurons

Long chain fatty acids (LCFAs) have been suggested to influence the activity of hypothalamic neurons, however, limited studies have attempted to identify the neurochemical phenotype of these neurons. We aimed to determine if physiological levels of LCFAs alter the electrical excitability of pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus of the hypothalamus. We utilised whole-cell patch-clamp electrophysiology on brain slice preparations from genetic mouse models where green fluorescent protein was expressed in either POMC or NPY expressing cells. All animals had undergone an overnight fast to replicate conditions in which fatty acids would usually increase. Bath application of LCFAs were found to predominantly inhibit POMC neurons and predominantly excite NPY neurons. Differences between oleic and palmitic acid were not observed. These results suggest that LCFAs in the cerebrospinal fluid exert an underlying orexigenic tone to key hypothalamic neurons known to regulate energy homeostasis.