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Although these changes contribute to the sympathetic response, how fasting evokes this plasticity is not known. Here we report these effects involve activation of GPR109A (HCAR2). The endogenous agonist of this G protein\u2013coupled receptor is \u03b2-hydroxybutyrate, a ketone body whose levels rise during fasting. In wild-type animals, 24-hour fasting increased AgRP-ir in adrenal chromaffin cells but this effect was absent in GPR109A knockout mice. GPR109A agonists increased AgRP-ir in isolated chromaffin cells through a GPR109A- and pertussis toxin\u2013sensitive pathway. Incubation of adrenal slices in nicotinic acid, a GPR109A agonist, mimicked the fasting-induced increase in the strength of the preganglionic \u2192 chromaffin cell synapse. Finally, reverse transcription polymerase chain reaction experiments confirmed the mouse adrenal medulla contains GPR109A messenger RNA. These results are consistent with the activation of a GPR109A signaling pathway located within the adrenal gland. Because fasting evokes epinephrine release, which stimulates lipolysis and the production of \u03b2-hydroxybutyrate, our results indicate that chromaffin cells are components of an autonomic-adipose-hepatic feedback circuit. Coupling a change in adrenal physiology to a metabolite whose levels rise during fasting is presumably an efficient way to coordinate the homeostatic response to food deprivation.<\/jats:p>","DOI":"10.1210\/endocr\/bqac077","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T00:53:47Z","timestamp":1653094427000},"source":"Crossref","is-referenced-by-count":4,"title":["The \u03b2-Hydroxybutyrate-GPR109A Receptor Regulates Fasting-induced Plasticity in the Mouse Adrenal Medulla"],"prefix":"10.1210","volume":"163","author":[{"given":"Rajesh","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Cell Biology & Anatomy, LSU Health Sciences Center , New Orleans, Louisiana 70112 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology & Anatomy, LSU Health Sciences Center , New Orleans, Louisiana 70112 , 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