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Decreased postnatal survival and altered body weight regulation in procolipase-deficient mice

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Author

Summary, in English

In vitro, pancreatic triglyceride lipase requires colipase to restore activity in the presence of inhibitors, like bile acids. Presumably, colipase performs the same function in vivo, but little data supports that notion. Other studies suggest that colipase or its proform, procolipase, may have additional functions in appetite regulation or in fat digestion during the newborn period when pancreatic triglyceride lipase is not expressed. To identify the physiological role of procolipase, we created a mouse model of procolipase deficiency. The Clps(-/-) mice appeared normal at birth, but unexpectedly 60% died within the first 2 weeks of life. The survivors had fat malabsorption as newborns and as adults, but only when fed a high fat diet. On a low fat diet, the Clps(-/-) mice did not have steatorrhea. The Clps(-/-) pups had impaired weight gain and weighed 30% less than Clps(+/+) or Clps(+/-) littermates. After weaning, the Clps(-/-) mice had normal rate of weight gain, but they maintained a reduced body weight compared with normal littermates even on a low fat diet. Despite the reduced body weight, the Clps(-/-) mice had a normal body temperature. To maintain their weight gain in the presence of steatorrhea, the Clps(-/-) mice had hyperphagia on a high fat diet. Clps(-/-) mice had normal intake on a low fat diet. We conclude that, in addition to its critical role in fat digestion, procolipase has essential functions in postnatal development and in regulating body weight set point.

Publishing year

2002

Language

English

Pages

7170-7177

Publication/Series

Journal of Biological Chemistry

Volume

277

Issue

9

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Basic Medicine

Status

Published

Research group

  • Appetite Regulation

ISBN/ISSN/Other

  • ISSN: 1083-351X