Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice.
This study generated pancreatic triglyceride lipase (PTL)-null mice to test the hypothesis that PTL-mediated hydrolysis of dietary triglyceride is necessary for efficient dietary cholesterol absorption. The PTL-/- mice grew normally and displayed similar body weight as their PTL+/+ littermates. Plasma lipid levels between animals of various PTL genotypes were similar when they were maintained on either a basal low fat diet or a western-type high fat/high cholesterol diet. Although the lack of a functional PTL delayed fat absorption during the initial hour of feeding a bolus load of olive oil containing [3H]triolein and [14C]cholesterol, the rate of [3H]triolein absorption was similar between PTL+/+ and PTL-/- mice after the initial 1-h period. Importantly, comparison of fecal fat content revealed similar overall fat absorption efficiency between PTL+/+ and PTL-/- mice. In contrast, the PTL-/- mice displayed significant decrease in both the rate and the amount of cholesterol absorbed after a single meal. The plasma appearance of [14C]cholesterol was found to be 75% lower (p < 0.0005) in PTL-/- mice compared with PTL+/+ mice after 4 h. The total amount of [14C]cholesterol excreted in the feces was 45% higher (p < 0.0004) in PTL-/- mice compared with PTL+/+ mice over a 24-h period. These results indicate that the delayed fat digestion due to PTL deficiency results in a significant reduction in cholesterol absorption, although other enzymes in the digestive tract may compensate for the lack of PTL in PTL-/- mice in fat digestion and absorption.
Huggins
Kevin W
KW
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Camarota
Lisa M
LM
Howles
Philip N
PN
Hui
David Y
DY
D000042:Absorption; D000483:Alleles; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D005223:Fats; D005243:Feces; D005838:Genotype; D006868:Hydrolysis; D015151:Immunoblotting; D008049:Lipase / Q000172:deficiency* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008957:Models, Genetic; D010179:Pancreas / Q000201:enzymology*; D010713:Phosphatidylcholines / Q000378:metabolism; D019518:Postprandial Period; D013997:Time Factors
D001647:Bile Acids and Salts; D018076:DNA, Complementary; D004041:Dietary Fats; D005223:Fats; D010713:Phosphatidylcholines; D002784:Cholesterol; D008049:Lipase