Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity.
OBJECTIVE
Cholecystokinin (CCK) is a satiation peptide released during meals in response to lipid intake; it regulates pancreatic digestive enzymes that are required for absorption of nutrients. We proposed that mice with a disruption in the CCK gene (CCK knockout [CCK-KO] mice) that were fed a diet of 20% butter fat would have altered fat metabolism.


METHODS
We used quantitative magnetic resonance imaging to determine body composition and monitored food intake of CCK-KO mice using an automated measurement system. Intestinal fat absorption and energy expenditure were determined using a noninvasive assessment of intestinal fat absorption and an open circuit calorimeter, respectively.


RESULTS
After consuming a high-fat diet for 10 weeks, CCK-KO mice had reduced body weight gain and body fat mass and enlarged adipocytes, despite the same level of food intake as wild-type mice. CCK-KO mice also had defects in fat absorption, especially of long-chain saturated fatty acids, but pancreatic triglyceride lipase did not appear to have a role in the fat malabsorption. Energy expenditure was higher in CCK-KO than wild-type mice, and CCK-KO mice had greater oxidation of carbohydrates while on the high-fat diet. Plasma leptin levels in the CCK-KO mice fed the high-fat diet were markedly lower than in wild-type mice, although levels of insulin, gastric-inhibitory polypeptide, and glucagon-like peptide-1 were normal.


CONCLUSIONS
CCK is involved in regulating the metabolic rate and is important for lipid absorption and control of body weight in mice placed on a high-fat diet.
Lo
Chun-Min
CM
Cincinnati Obesity Research Center, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio 45237, USA.
King
Alexandra
A
Samuelson
Linda C
LC
Kindel
Tammy Lyn
TL
Rider
Therese
T
Jandacek
Ronald J
RJ
Raybould
Helen E
HE
Woods
Stephen C
SC
Tso
Patrick
P
D050154:Adiposity; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002079:Butter; D002151:Calorimetry; D002766:Cholecystokinin / Q000172:deficiency* / Q000235:genetics; D004041:Dietary Fats / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004435:Eating; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D007408:Intestinal Absorption; D020738:Leptin / Q000097:blood; D008049:Lipase / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D015430:Weight Gain
D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D020738:Leptin; D002079:Butter; D002766:Cholecystokinin; D008049:Lipase