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  The beta-Hydroxybutyrate-GPR109A Receptor Regulates Fasting-induced Plasticity in the Mouse Adrenal Medulla

Gupta, R., Wang, M., Ma, Y., Offermanns, S., & Whim, M. D. (2022). The beta-Hydroxybutyrate-GPR109A Receptor Regulates Fasting-induced Plasticity in the Mouse Adrenal Medulla. ENDOCRINOLOGY, 163(7): bqac077. doi:10.1210/endocr/bqac077.

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Gupta, Rajesh, Author
Wang, Manqi, Author
Ma, Yunbing, Author
Offermanns, Stefan1, Author              
Whim, Matthew D., Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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 Abstract: During fasting, increased sympathoadrenal activity leads to epinephrine release and multiple forms of plasticity within the adrenal medulla including an increase in the strength of the preganglionic -> chromaffin cell synapse and elevated levels of agouti-related peptide (AgRP), a peptidergic cotransmitter in chromaffin cells. 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-coupled receptor is beta-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-sensitive pathway. Incubation of adrenal slices in nicotinic acid, a GPR109A agonist, mimicked the fasting-induced increase in the strength of the preganglionic -> 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 beta-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.

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 Dates: 2022-05-202022-07-01
 Publication Status: Published in print
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 Identifiers: ISI: 000809611900002
DOI: 10.1210/endocr/bqac077
PMID: 35595517
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Title: ENDOCRINOLOGY
Source Genre: Journal
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Pages: - Volume / Issue: 163 (7) Sequence Number: bqac077 Start / End Page: - Identifier: ISSN: 0013-7227