Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity.

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.

• Authors: Chun-Min Lo, Alexandra King, Linda C Samuelson, Tammy Lyn Kindel, Therese Rider, Ronald J Jandacek, Helen E Raybould, Stephen C Woods, Patrick Tso
• Journal: Gastroenterology (Gastroenterology) Vol. 138 Issue 5 Pg. 1997-2005 (May 2010) ISSN: 1528-0012 [Electronic] United States
• PMID: 20117110 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Dietary Fats
• Fatty Acids
• Leptin
• Butter
• Cholecystokinin
• Lipase

Topics

• Adiposity
• Animals
• Biomarkers (blood)
• Butter
• Calorimetry
• Cholecystokinin (deficiency, genetics)
• Dietary Fats (blood, metabolism)
• Disease Models, Animal
• Eating
• Energy Metabolism
• Fatty Acids (metabolism)
• Intestinal Absorption
• Leptin (blood)
• Lipase (metabolism)
• Magnetic Resonance Imaging
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity
• Obesity (genetics, metabolism, physiopathology, prevention & control)
• Time Factors
• Weight Gain