Effects of the Saturated Fatty Acid Palmitate on Neuroinflammation, ER Stress, and Pomc mRNA Expression in Hypothalamic mHypoA-POMC/GFP Neurons

Dietary fats can modulate brain function. How free fatty acids (FFAs) alter hypothalamic pro-opiomelanocortin (POMC) neurons remain undefined. The saturated FFA, palmitate, increased neuroinflammatory and ER stress markers, as well as Pomc mRNA levels, but did not affect insulin signalling, in mHypoA-POMC/GFP-2 neurons. This effect was mediated through the MAPK JNK and ERK. Further, the increase in Pomc was dependent on palmitoyl-coA synthesis, but not de novo ceramide synthesis, as inhibition of SPT enhanced palmitate-induced Pomc expression, while methylpalmitate had no effect. While palmitate concomitantly induces neuroinflammation and ER stress, these effects were independent of changes in Pomc expression. Palmitate thus has direct acute effects on Pomc, which appears to be important for negative feedback, but not directly related to neuroinflammation. The monounsaturated FFA oleate completely blocked the palmitate-mediated increase in neuroinflammation, ER stress, and Pomc mRNAs. This study provides insight into the complex central metabolic regulation by FFAs.M.Sc.2018-11-13 00:00:0