Disruption of the murine intestinal alkaline phosphatase gene Akp3 impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis.
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.
Nakano
Takanari
T
Dept. of Biochemistry, Faculty of Medicine, Faculty of Health and Medical Care, Saitama Medical Univ., Saitama, Japan 350-0495.
Inoue
Ikuo
I
Koyama
Iwao
I
Kanazawa
Kenta
K
Nakamura
Koh-Ichi
K
Narisawa
Sonoko
S
Tanaka
Kayoko
K
Akita
Masumi
M
Masuyama
Taku
T
Seo
Makoto
M
Hokari
Shigeru
S
Katayama
Shigehiro
S
Alpers
David H
DH
Millán
José Luis
JL
Komoda
Tsugikazu
T
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000201:enzymology*; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000254:growth & development*; D050356:Lipid Metabolism / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D004041:Dietary Fats; D014280:Triglycerides; D011092:Polyethylene Glycols; D008071:Lipoprotein Lipase; C520837:Akp3 protein, mouse; D000469:Alkaline Phosphatase; C016811:tyloxapol