Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels.
Immunocytochemistry showed expression of aquaporin-1 (AQP1) water channels at sites involved in dietary fat processing, including intrahepatic cholangiocytes, gallbladder, pancreatic microvascular endothelium, and intestinal lacteals. To determine whether AQP1 has a role in dietary fat digestion and/or absorption, mice were placed on a diet that contained 50% fat. Whereas wild-type mice (3-3.5 wk of age, 10-12 g) gained 49 +/- 5% (SE, n = 50) body weight in 8 days, and heterozygous mice gained 46 +/- 4%, AQP1 null mice gained only 4 +/- 3%; weights became similar after return to a 6% fat diet after 6 days. The null mice on a high-fat diet acquired an oily appearance, developed steatorrhea with increased stool triglyceride content, and manifested serum hypotriglyceridemia. Supplementation of the high-fat diet with pancreatic enzymes partially corrected the decreased weight gain in null mice. Absorption of [(14)C]oleic acid from small intestine was not affected by AQP1 deletion, as determined by blood radioactivity after duodenal infusion. Lipase activity in feces and small intestine was remarkably greater in AQP1 null than wild-type mice on low- and high-fat diets. Fluid collections done in older mice (that are less sensitive to a high-fat diet) by ductal cannulation showed threefold increased pancreatic fluid flow in response to secretin/cholecystokinin, but volumes, pH, and amylase activities were affected little by AQP1 deletion, nor were bile flow rates and bile salt concentrations. Together, these results establish a dietary fat misprocessing defect in AQP1 null mice.
Ma
T
T
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143-0521, California, USA.
Jayaraman
S
S
Wang
K S
KS
Song
Y
Y
Yang
B
B
Li
J
J
Bastidas
J A
JA
Verkman
A S
AS
D000367:Age Factors; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000172:deficiency* / Q000235:genetics; D001835:Body Weight / Q000502:physiology; D002446:Celiac Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004041:Dietary Fats / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004066:Digestive System Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004435:Eating / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D005526:Food, Formulated / Q000009:adverse effects; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D008049:Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D020799:Pancrelipase / Q000494:pharmacology
C496021:Aqp1 protein, mouse; D020346:Aquaporins; D004041:Dietary Fats; D005227:Fatty Acids; D051398:Aquaporin 1; D020799:Pancrelipase; D008049:Lipase