Characterization of mice lacking the gene for cholecystokinin

Abstract

acts peripherally as a satiating peptide released during meals in response to lipid feeding and centrally functions in the modulation of feeding, exploratory, and memory activities. The present study determined metabolic parameters, food intake, anxiety-like behaviors, and cognitive function in mice lacking the CCK gene. We studied intestinal fat absorption, body composition, and food intake of CCK knockout (CCK-KO) mice by using the noninvasive measurement of intestinal fat absorption along with quantitative magnetic resonance (QMR) imaging and the DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity and conducting elevated plus-maze and Morris watermaze tests with these mice. Compared with wild-type (WT) littermate controls, CCK-KO mice had normal food intake, fat absorption, body weight, and body mass. CCK-KO mice ate more food than control animals during the light period and less food during the dark period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and impaired spatial memory in the Morris water maze test. We conclude that CCK is involved in metabolic rate and is important for memory and exploration. CCK is intimately involved in multiple processes related to cognitive function and food intake regulation. cholecystokinin 1 receptor; cholecystokinin 2 receptor; cognitive behaviors CCK OCCURS as a carboxyl terminally amidated peptide that exists in several possible lengths (43,58,66). In rats and mice, the predominant circulating forms include cholecystokinin octapeptide (CCK-8) and CCK-22, whereas larger molecular forms (CCK-33 and CCK-58) are also present in human and canine plasma (42,61,38,63,16). These molecular forms are processed from a 115-amino acid preprohormone product of the gene residing in chromosome 3 in rodents (13, 57). Intestinal endocrine cells secrete a mixture of medium-sized CCK forms, while central and peripheral neurons mainly release sulfated forms of 62). In response to consumption of either lipid and protein, CCK is produced and secreted by intestinal I cells (41). The release of CCK from neurons is caused by potassium ion-induced depolarization (15). Peripheral CCK is involved in modulating intestinal motility, stimulating pancreatic enzyme secretion, enhancing gallbladder contraction, and regulating meal size (11,21,24,29,48,56,64,69).CCK is also a neurotransmitter in many areas of the nervous system (6). Intraperitoneal or central administration of either purified CCK extracts or synthetic CCK-8 to fasted rats reduces food intake (22,33,37,54), and this is manifested by a reduction of meal size as opposed to reduced frequency of meals (22,37). Two types of CCK receptors (CCK1...

Lipid transport in cholecystokinin knockout mice

“…LFD-fed CCK-KO mice have comparable body weight and fat mass to WT, but HFD-fed CCK-KO mice are shown again to be resistant to HFD-induced obesity which is consistent with previous reports [39, 41]. The present study demonstrates that HFD-fed CCK-KO mice with comparable fat absorption have reduced body weight and fat mass.…”

“…Male CCK-KO mice and their wild-type (WT) littermates were generated onto a C57BL/6J genetic background [39–41] and housed in an AAALAC-accredited facility under conditions of controlled illumination (12:12-h light-dark cycle, lights on from 0600 to 1800 h). All animal protocols were approved by the University of Cincinnati Institutional Animal Care and Use Committee.…”

“…Fat and lean body masses were determined using an EchoMRI whole body composition analyzer (Houston, TX) [39, 41]. After 10 wk on LFD or the HFD, fat pads, liver and plasma were carefully collected and weighed from 5-h fasted mice.…”

Life‐span extension by dietary restriction is mediated by NLP‐7 signaling and coelomocyte endocytosis inC. elegans

“…Exogenous administration of CCK decreases food intake in rats (38) and humans (39). However, mice lacking the gene for CCK have normal body weight, body mass, and fat absorption as compared with wild-type littermate controls (40); differences in longevity were not examined. Food-restricted rats showed increased plasma CCK, which suggests a physiological role for CCK in the adaptation to reduced food ingestion (41).…”

CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor

“…Body composition of unanesthetized mice was measured by quantitative magnetic resonance imaging using EchoMRI (Echo Medical Systems, Houston, TX) as described by Lo et al (36). Indirect calorimetry was performed by the PhysioScan System from AccuScan Instruments as described previously (36,48). Volumes of O 2 consumed and CO2 produced were determined as ml·kg body wt Ϫ1 ·min Ϫ1 , and heat production was determined as calories·kg body wt Ϫ1 ·h Ϫ1 .…”