RT Journal Article
SR Electronic
T1 Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.17.254862
DO 10.1101/2020.08.17.254862
A1 Juliana Bezerra Medeiros de Lima
A1 Lucas Kniess Debarba
A1 Manal Khan
A1 Chidera Ubah
A1 Olesya Didyuk
A1 Iven Ayyar
A1 Madelynn Koch
A1 Marianna Sadagurski
YR 2020
UL http://biorxiv.org/content/early/2020/08/17/2020.08.17.254862.abstract
AB Growth hormone (GH) receptor (GHR), expressed in different brain regions, is known to participate in the regulation of whole-body energy homeostasis and glucose metabolism. However, GH activation of these GHR-expressing neurons is less studied. We have generated a novel GHR-driven Cre recombinase transgenic mouse line (GHRcre) in combination with the floxed tdTomato reporter mouse line we tracked and activated GHR-expressing neurons in different regions of the brain. We focused on neurons of the hypothalamic arcuate nucleus (ARC) where GHR was shown to elicit a negative feedback loop that regulates GH production. We found that ARCGHR+ neurons are co-localized with AgRP, GHRH, and somatostatin neurons, which were activated by GH stimulation. Using designer receptors exclusively activated by designer drugs (DREADDs) to control GHRARC neuronal activity, we revealed that activation of GHRARC neurons was sufficient in regulating distinct aspects of energy balance and glucose metabolism. Overall, our study provides a novel mouse model to study in vivo regulation and physiological function of GHR-expressing neurons in various brain regions. Furthermore, we identified for the first time specific neuronal population that responds to GH and directly linked it to metabolic responses in vivo.Competing Interest StatementThe authors have declared no competing interest.CNScentral nervous systemGHgrowth hormoneGHRgrowth hormone receptorSTAT5signal transducer and activator of transcription 5POMCproopiomelanocortinARCarcuate nucleus of the hypothalamusDMHdorsomedial hypothalamic nucleusLHAlateral hypothalamusPVHparaventricular hypothalamic nucleusSSTsomatostatinGHRHgrowth hormone releasing hormoneAgRPagouti-related peptide