Accelerated fat absorption in intestinal alkaline phosphatase knockout mice.
Intestinal alkaline phosphatase (IAP) is the most ancestral of the tissue-specific members of the AP gene family. Several studies have suggested an absorptive function for IAP, but in vivo data to this effect have been lacking. We inactivated the mouse IAP gene in embryo-derived stem cells and generated mice homozygous for the null mutation. The mice were macroscopically and histologically normal and fertile and showed no difference from the wild-type controls under normal laboratory conditions. However, when maintained long-term on a high-fat diet, the IAP-deficient mice showed faster body weight gain than did control animals. Histological examination revealed an accelerated transport of fat droplets through the intestinal epithelium and elevation of serum triglyceride levels in the IAP-deficient mice compared to wild-type mice. Our study suggests that IAP participates in a rate-limiting step regulating fat absorption.
Narisawa
Sonoko
S
The Burnham Institute, La Jolla, California 92037, USA.
Huang
Lei
L
Iwasaki
Arata
A
Hasegawa
Hideaki
H
Alpers
David H
DH
Millán
José Luis
JL
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins; D020868:Gene Silencing; D018390:Gene Targeting; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D013234:Stem Cells / Q000502:physiology; D014280:Triglycerides / Q000097:blood
D000951:Antigens, Neoplasm; D004041:Dietary Fats; D058851:GPI-Linked Proteins; D014280:Triglycerides; C063088:ALPI protein, human; D000469:Alkaline Phosphatase