Central PACAP mediates the sympathetic effects of leptin in a tissue-specific manner.

Abstract

We previously demonstrated that the peptidergic neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) affects the autonomic system and contributes to the control of metabolic and cardiovascular functions. Previous studies have demonstrated the importance of centrally-mediated sympathetic effects of leptin for obesity-related hypertension. Here we tested whether PACAP signaling in the brain is implicated in leptin-induced sympathetic excitation and appetite suppression. In anesthetized mice, intracerebroventricular (ICV) pre-treatment with PACAP6-38, an antagonist of the PACAP receptors (PAC1-R and VPAC2), inhibited the increase in white adipose tissue sympathetic nerve activity (WAT-SNA) produced by ICV leptin (2μg). In contrast, leptin-induced stimulation of renal sympathetic nerve activity (RSNA) was not affected by ICV pre-treatment with PACAP6-38. Moreover, in PACAP-deficient (Adcyap1-/-) mice, ICV leptin-induced WAT-SNA increase was impaired, whereas RSNA response was preserved. The reductions in food intake and body weight evoked by ICV leptin were attenuated in Adcyap1-/- mice. Our data suggest that hypothalamic PACAP signaling plays a key role in the control by leptin of feeding behavior and lipocatabolic sympathetic outflow, but spares the renal sympathetic traffic.

• Authors: M Tanida, A Hayata, N Shintani, N Yamamoto, Y Kurata, T Shibamoto, D A Morgan, K Rahmouni, H Hashimoto
• Journal: Neuroscience (Neuroscience) Vol. 238 Pg. 297-304 (May 15 2013) ISSN: 1873-7544 [Electronic] United States
• PMID: 23454538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Adcyap1 protein, mouse
• Leptin
• Peptide Fragments
• Pituitary Adenylate Cyclase-Activating Polypeptide
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
• pituitary adenylate-cyclase-activating-peptide (6-38)

Topics

• Adipose Tissue, White (drug effects, innervation, metabolism)
• Animals
• Body Weight (drug effects)
• Eating (drug effects)
• Hypothalamus (drug effects, metabolism)
• Injections, Intraventricular
• Kidney (drug effects, innervation, metabolism)
• Leptin (pharmacology)
• Male
• Mice
• Mice, Knockout
• Organ Specificity
• Peptide Fragments (pharmacology)
• Pituitary Adenylate Cyclase-Activating Polypeptide (genetics, metabolism, pharmacology)
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide (metabolism)
• Sympathetic Nervous System (drug effects, physiology)