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1 Biochemistry, Saitama Medical School, Irumagunn, Saitama, Japan
2 Dept. of Diabetes and Endocrinology, Saitama Medical University, Iruma-gun, Saitama, Japan
3 School of Medical Technology and Health, Faculty of Health and Medical Care, Saitama Medical University, Iruma-gun, Iruma-gun, Japan
4 Diabetes and Endocrinology, Saitama Medical University, United States
5 Burnham Institute for Medical Research, La Jolla, California, United States
6 Dept. of Morphology, Saitama Medical University, Iruma-gun, Saitama, Japan
7 Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Kanagawa, Japan
8 Biochemistry, Saitama Medical University, United States
9 Medicine, University of Washington School of Medicine, St. Louis, Missouri, United States
* To whom correspondence should be addressed. E-mail: tkalp1lp{at}saitama-med.ac.jp.
Intestinal alkaline phosphatase (IAP) is involved in the process of fat absorption, a conclusion confirmed by an altered lipid transport and a faster body weight gain from 10 to 30 weeks in both male and female mice with a homozygous null mutation of the IAP coding gene (Akp3-/- mice). This study was aimed to delineate the accelerated lipid absorption in male (Akp3-/- mice morphologically and quantitatively. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 h vs. 4 h for knockout and wild-type, respectively) and an approximately two-fold increase in serum triacylglycerol concentration in Akp3-/- mice injected with a lipolysis inhibitor, Triton WR-1339. A corn oil load induced the three-fold enlargement of the Golgi vacuoles in male wild-type, but not in Akp3-/- mice, indicating that absorbed lipids rarely reached the Golgi complex and the transcytosis of lipid droplets does not follow the normal pathway in the male Akp3-/- mice. Force feeding an exaggerated fat intake by a 30% fat chow for 10 weeks induced obesity in both male Akp3-/- and wild-type mice and therefore no phenotypic difference was observed between the two. On the other hand, the forced high fat chow induced an 18% greater body weight gain, hepatic steatosis, and visceral fat accumulation in female Akp3-/- mice, but not in the female wild-type controls. These results provide further evidence that IAP is involved in the regulation of lipid absorption process and that its absence leads to progressive metabolic abnormalities in certain fat forced conditions.
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  G. H. Hansen, L.-L. Niels-Christiansen, L. Immerdal, B. T. Nystrom, and E. M. Danielsen Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1325 - G1332. [Abstract] [Full Text] [PDF]
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S. Narisawa, M. F. Hoylaerts, K. S. Doctor, M. N. Fukuda, D. H. Alpers, and J. L. Millan A novel phosphatase upregulated in Akp3 knockout mice Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G1068 - G1077. [Abstract] [Full Text] [PDF]
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