title: CCK Response Deficiency in Synphilin-1 Transgenic Mice.
abstract: Previously, we have identified a novel role for the cytoplasmic protein, synphilin-1(SP1), in the controls of food intake and body weight in both mice and Drosophila. Ubiquitous overexpression of human SP1 in brain neurons in transgenic mice results in hyperphagia expressed as an increase in meal size. However, the mechanisms underlying this action of SP1 remain to be determined. Here we investigate a potential role for altered gut feedback signaling in the effects of SP1 on food intake. We examined responses to peripheral administration of cholecytokinin (CCK), amylin, and the glucagon like peptide-1 (GLP-1) receptor agonist, exendin-4. Intraperitoneal administration of CCK at doses ranging from 1-10 nmol/kg significantly reduced glucose intake in wild type (WT) mice, but failed to affect intake in SP1 transgenic mice. Moreover, there was a significant attenuation of CCK-induced c-Fos expression in the dorsal vagal complex in SP1 transgenic mice. In contrast, WT and SP1 transgenic mice were similarly responsive to both amylin and exendin-4 treatment. These studies demonstrate that SP1 results in a CCK response deficiency that may contribute to the increased meal size and overall hyperphagia in synphillin-1 transgenic mice.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, United States of America.
authors.forename: Wanli W
authors.initials: WW
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Megan
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, United States of America.
authors.forename: Dejun
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Pique P
authors.initials: PP
authors.lastname: Choi
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Moghadam
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, United States of America.
authors.forename: Tianxia
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002766:Cholecystokinin / Q000737:chemistry*; D003593:Cytoplasm / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D000077270:Exenatide; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D006801:Humans; D006963:Hyperphagia / Q000473:pathology; D007263:Infusions, Parenteral; D007413:Intestinal Mucosa / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000235:genetics; D010455:Peptides / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D014688:Venoms / Q000737:chemistry; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D009419:Nerve Tissue Proteins; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; C118958:SNCAIP protein, human; C498464:Sncaip protein, mouse; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists