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

D'Agostino, D; Cordle, RA; Kullman, J; Erlanson-Albertsson, Charlotte LU ; Muglia, LJ and Lowe, ME (2002) In Journal of Biological Chemistry 277(9). p.7170-7177
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
277
issue
9
pages
7170 - 7177
publisher
ASBMB
external identifiers
  • wos:000174104300055
  • pmid:11751900
  • scopus:0036510574
ISSN
1083-351X
DOI
10.1074/jbc.M108328200
language
English
LU publication?
yes
id
b7fd1de2-dc33-4755-ba3c-891e469bf753 (old id 342563)
date added to LUP
2007-08-15 14:03:00
date last changed
2017-08-06 03:32:36
@article{b7fd1de2-dc33-4755-ba3c-891e469bf753,
  abstract     = {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.},
  author       = {D'Agostino, D and Cordle, RA and Kullman, J and Erlanson-Albertsson, Charlotte and Muglia, LJ and Lowe, ME},
  issn         = {1083-351X},
  language     = {eng},
  number       = {9},
  pages        = {7170--7177},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Decreased postnatal survival and altered body weight regulation in procolipase-deficient mice},
  url          = {http://dx.doi.org/10.1074/jbc.M108328200},
  volume       = {277},
  year         = {2002},
}