Dietary fat ingestion activates β-endorphin neurons in the hypothalamus

► The opioid system regulates hedonic behavior for high-fat or sweetened food. ► We examine whether dietary fat itself could stimulate the opioid system. ► Gustatory stimulus of fat could promote the release of opioid peptide, β-endorphin. ► Dietary fat stimulates β-endorphin release promoting food ingestion. The opioid system regulates food choice, consumption, and reinforcement processes, especially for palatable meals such as fatty food. β-Endorphin is known as an endogenous opioid peptide produced in neurons of the hypothalamus. In this study, we found that Intralipid (fat emulsion) ingestion increased c-fos expression in β-endorphin neurons. However, intragastric infusion of Intralipid only slightly increased c-fos expression 2h after infusion. Further, dissection of glossopharyngeal nerve, innervating posterior tongue taste buds, partially but significantly decreased the Intralipid-induced c-fos expression. These results indicate that mainly the orosensory stimulation from fat may activate β-endorphin neurons, thereby promoting β-endorphin release.