CB1Rs in VMH neurons regulate glucose homeostasis but not body weight

Carlos M. Castorena, Alexandre Caron, Natalie J. Michael, Newaz I. Ahmed, Amanda G. Arnold, Jiwon Lee, Charlotte Lee, Chelsea Limboy, Arely Salazar Tinajero, Madison Granier, Simeng Wang, Jay D. Horton, William L. Holland, Syann Lee, Chen Liu, Teppei Fujikawa, Joel K. Elmquist

Research output: Contribution to journalArticlepeer-review

Abstract

Cannabinoid 1 receptor (CB1R) inverse agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that the deletion of CB1Rs in the VMH did not affect body weight in chow- and high-fat diet-fed male and female mice. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse agonist SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice.

Original languageEnglish (US)
Pages (from-to)E146–E155
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume321
Issue number1
DOIs
StatePublished - Jul 2021
Externally publishedYes

Keywords

  • CB1R
  • Glucose metabolism
  • Metabolic homeostasis
  • SR141716
  • VMH

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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