title: 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: Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan. mtanida@kanazawa-med.ac.jp
authors: M
authors: M
authors: Tanida
authors: A
authors: A
authors: Hayata
authors: N
authors: N
authors: Shintani
authors: N
authors: N
authors: Yamamoto
authors: Y
authors: Y
authors: Kurata
authors: T
authors: T
authors: Shibamoto
authors: D A
authors: DA
authors: Morgan
authors: K
authors: K
authors: Rahmouni
authors: H
authors: H
authors: Hashimoto
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D010446:Peptide Fragments / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: C495402:Adcyap1 protein, mouse; D020738:Leptin; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38)