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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/G1439    most recent 00331.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Nakano, T. Articles by Komoda, T. Search for Related Content PubMed PubMed Citation Articles by Nakano, T. Articles by Komoda, T.

MUCOSAL BIOLOGY

Disruption of the murine intestinal alkaline phosphatase gene Akp3 impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis

Departments of ¹Biochemistry, ²Diabetes and Endocrinology, and ⁵Morphology, Faculty of Medicine, and ³School of Medical Technology and Health, Faculty of Health and Medical Care, Saitama Medical University, Saitama, Japan; ⁴Burnham Institute for Medical Research, La Jolla, California; ⁶Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco, Kanagawa, Japan; and ⁷Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Submitted 24 July 2006 ; accepted in final form 3 October 2006

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 wk in both male and female mice with a homozygous null mutation of the IAP coding gene (Akp3^–/– mice). This study was aimed to delineate morphologically and quantitatively the accelerated lipid absorption in male Akp3^–/– mice. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 vs. 4 h for Akp3^–/– and wild-type mice, respectively) and an approximately twofold increase in serum triacylglycerol concentration in Akp3^–/– mice injected with a lipolysis inhibitor, Triton WR-1339. A corn oil load induced the threefold enlargement of the Golgi vacuoles in male wild-type mice but not in Akp3^–/– mice, indicating that absorbed lipids rarely reached the Golgi complex and that the transcytosis of lipid droplets does not follow the normal pathway in male Akp3^–/– mice. Force feeding an exaggerated fat intake by a 30% fat chow for 10 wk 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 female wild-type controls. These results provide further evidence that IAP is involved in the regulation of the lipid absorption process and that its absence leads to progressive metabolic abnormalities in certain fat-forced conditions.

fat absorption; metabolic abnormality; obesity; small intestine

This article has been cited by other articles:

				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]

				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]