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Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity. Gastroenterology 2010 May;138(5):1997-2005

Date

02/02/2010

Pubmed ID

20117110

Pubmed Central ID

PMC3049264

DOI

10.1053/j.gastro.2010.01.044

Scopus ID

2-s2.0-77951692010 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

BACKGROUND & AIMS: 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.

Author List

Lo CM, King A, Samuelson LC, Kindel TL, Rider T, Jandacek RJ, Raybould HE, Woods SC, Tso P

Author

Tammy Lyn Kindel MD, PhD Associate Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adiposity
Animals
Biomarkers
Butter
Calorimetry
Cholecystokinin
Dietary Fats
Disease Models, Animal
Eating
Energy Metabolism
Fatty Acids
Intestinal Absorption
Leptin
Lipase
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity
Obesity
Time Factors
Weight Gain