Faculty Collaboration Database

Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate cyclase-activating polypeptide induces hypophagia and thermogenesis. Am J Physiol Regul Integr Comp Physiol 2011 Dec;301(6):R1625-34

Date

10/01/2011

Pubmed ID

21957159

Pubmed Central ID

PMC3233848

DOI

10.1152/ajpregu.00334.2011

Scopus ID

2-s2.0-82755192274 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

Numerous studies have demonstrated that the hypothalamic ventromedial nuclei (VMN) regulate energy homeostasis by integrating and utilizing behavioral and metabolic mechanisms. The VMN heavily express pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptors (PAC1R). Despite the receptor distribution, most PACAP experiments investigating affects on feeding have focused on intracerebroventricular administration or global knockout mice. To identify the specific contribution of PACAP signaling in the VMN, we injected PACAP directly into the VMN and measured feeding behavior and indices of energy expenditure. Following an acute injection of PACAP, nocturnal food intake was significantly reduced for 6 h after injections without evidence of malaise. In addition, PACAP-induced suppression of feeding also occurred following an overnight fast and could be blocked by a specific PAC1R antagonist. Metabolically, VMN-specific injections of PACAP significantly increased both core body temperature and spontaneous locomotor activity with a concurrent increase in brown adipose uncoupling protein 1 mRNA expression. To determine which signaling pathways were responsive to PACAP administration into the VMN, we measured mRNA expression of well-characterized hypothalamic neuropeptide regulators of feeding. One hour after PACAP administration, expression of pro-opiomelanocortin mRNA was significantly increased in the arcuate nuclei (ARC), with no changes in neuropeptide Y and agouti-related polypeptide mRNA levels. This suggests that PAC1R expressing VMN neurons projecting to pro-opiomelanocortin neurons contribute to hypophagia by involving melanocortin signaling. While the VMN also abundantly express PACAP protein, the present study demonstrates that PACAP input to the VMN can influence the control of energy homeostasis.

Author List

Resch JM, Boisvert JP, Hourigan AE, Mueller CR, Yi SS, Choi S

Author

Sujean Choi PhD in the School of Allied Health department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Eating
Gene Expression Regulation
Male
Pituitary Adenylate Cyclase-Activating Polypeptide
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
Thermogenesis
Ventromedial Hypothalamic Nucleus