The effects of oleic - acid ( OA ) on distinct populations of neurons in the hypothalamic arcuate nucleus ( ARC ) are dependent on extracellular glucose levels

Pharmacological manipulation of fatty acid metabolism in the hypothalamic arcuate nucleus (ARC) alters energy balance and glucose homeostasis. Thus, we tested the hypotheses that distinctive populations of ARC neurons are oleic-acid (OA) sensors that exhibit a glucose dependency, independent of whether some of these OA sensors are also glucose sensing neurons. We used patch clamp recordings to investigate the effects of OA on ARC neurons in brain slices from 14 21 d Sprague-Dawley (SD) rats. Additionally, we recorded spontaneous discharge rate in ARC neurons in 8 week old fed and fasted SD rats in vivo. Patch clamp studies showed that in 2.5 mM glucose 12 of 94 (13%) ARC neurons were excited by 2 μM OA (OA-excited or OAE neurons) while 6 of 94 (6%) were inhibited (OA-inhibited2.5 or OAI2.5 neurons). In contrast, in 0.1 mM glucose, OA inhibited 6 of 20 (30%) ARC neurons (OAI0.1 neurons); none were excited. None of the OAI0.1 neurons responded to OA in 2.5 mM glucose. Thus, OAI2.5 and OAI0.1 neurons are distinct. Similarly, in 7 of 20 fed rats (35%) the overall response was OAElike, while in 3 of 20 (15%) it was OAI-like. In contrast, in fasted rats only OAI-like response were observed (3 of 15; 20%). There was minimal overlap between OA sensing neurons and glucose sensing neurons. In conclusion, OA regulated 3 distinct subpopulations of ARC neurons in a glucose-dependent fashion. These data suggest that an interaction between glucose and fatty acids regulates OA sensing in ARC neurons.