Cholecystokinin Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity

Chun Min Lo, Alexandra King, Linda C. Samuelson, Tammy Lyn Kindel, Therese Rider, Ronald J. Jandacek, Helen E Raybould, Stephen C. Woods, Patrick Tso

Research output: Contribution to journalArticle

39 Scopus 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.

Original languageEnglish (US)
Pages (from-to)1997-2005
Number of pages9
JournalGastroenterology
Volume138
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • CCK Receptor
  • Cholecystokinin
  • Fat Absorption
  • Indirect Calorimetry

ASJC Scopus subject areas

  • Gastroenterology

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    Lo, C. M., King, A., Samuelson, L. C., Kindel, T. L., Rider, T., Jandacek, R. J., Raybould, H. E., Woods, S. C., & Tso, P. (2010). Cholecystokinin Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity. Gastroenterology, 138(5), 1997-2005. https://doi.org/10.1053/j.gastro.2010.01.044