Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors.
Prior data demonstrated differential roles for cholecystokinin (CCK)1 receptors in maintaining energy balance in rats and mice. CCK1 receptor deficiency results in hyperphagia and obesity of Otsuka Long-Evans Tokushima Fatty (OLETF) rats but not in mice. To ascertain the role of CCK1 receptors in high-fat-diet (HFD)-induced obesity, we compared alterations in food intake, body weight, fat mass, plasma glucose, and leptin levels, and patterns of hypothalamic gene expression in OLETF rats and mice lacking CCK1 receptors in response to a 10-wk exposure to HFD. Compared with Long-Evans Tokushima Otsuka (LETO) control rats, OLETF rats on HFD had sustained overconsumption over the 10-wk period. High fat feeding resulted in greater increases in body weight and plasma leptin levels in OLETF than in LETO rats. In situ hybridization determinations revealed that, while HFD reduced neuropeptide Y (NPY) mRNA expression in both the arcuate nucleus (Arc) and the dorsomedial hypothalamus (DMH) of LETO rats, HFD resulted in decreased NPY expression in the Arc but not in the DMH of OLETF rats. In contrast to these results in OLETF rats, HFD increased food intake and induced obesity to an equal degree in both wild-type and CCK1 receptor(-/-) mice. NPY gene expression was decreased in the Arc in response to HFD, but was not detectable in the DMH in both wild-type and CCK1 receptor(-/-) mice. Together, these data provide further evidence for differential roles of CCK1 receptors in the controls of food intake and body weight in rats and mice.
Bi
Sheng
S
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205, USA. sbi@jhmi.edu
Chen
Jie
J
Behles
R Ryan
RR
Hyun
Jayson
J
Kopin
Alan S
AS
Moran
Timothy H
TH
D000273:Adipose Tissue / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism; D017403:In Situ Hybridization; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000096:biosynthesis; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D015347:RNA Probes; D051381:Rats; D020334:Rats, Inbred OLETF; D043886:Receptor, Cholecystokinin A / Q000096:biosynthesis* / Q000235:genetics
D001786:Blood Glucose; D004041:Dietary Fats; D020738:Leptin; D009478:Neuropeptide Y; D015347:RNA Probes; D043886:Receptor, Cholecystokinin A; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone