Disrupting the ghrelin-growth hormone axis limits ghrelin's orexigenic but not glucoregulatory actions

• DOI: 10.1016/j.molmet.2021.101258
• Publication Date: 2021-05-21T04:43:15Z
• Authors: Deepali Gupta; Anna M. Patterson; Sherri Osborne-La...; Angie L. Bookout; Salil Varshney; Kripa Shankar; Omprakash Singh; Nathan P. Metzger; Corine P. Richard; Steven C. Wyler; Joel K. Elmquist; Jeffrey M. Zigman
• Keywords: Orexigenic

Acyl-ghrelin regulates eating, body weight, blood glucose, and GH secretion upon binding to its receptor GHSR (growth hormone secretagogue receptor; ghrelin receptor). is distributed in several brain regions some peripheral cell-types including pituitary somatotrophs. The objective of the current study was determine functional significance acyl-ghrelin's action on GHSR-expressing somatotrophs mediating metabolic actions. GH-IRES-Cre mice loxP-flanked (floxed) were newly developed then crossed one another generate that lacked selectively from Following validation with somatotroph-selective deletion, responses these control littermates assessed following both acute chronic acyl-ghrelin administration, a 24-h fast, prolonged 60% caloric restriction protocol modeling starvation. In single injection failed induce or increase food intake, unlike wild-type other littermate groups. However, usual glucose response bolus preserved. Similarly, s.c. administration deletion plasma GH, weight. Physiologically elevating via fast also raise resulted limited hyperphagic reintroduction although those nonetheless did not exhibit an exaggerated reduction glucose. 15-day which provided only 40% daily calories life-threatening hypoglycemia. These results reveal direct engagement required for acutely stimulate actions delivery physiological elevations GH. suggest intake weight are reliant activation GHSRs expressed Furthermore, glucoregulatory – particular, when administered, prevent small drops avert hypoglycemia during acute-on-chronic do depend expression by