INTESTINAL EXPRESSION OF HUMAN APOLIPOPROTEIN A-IV IN TRANSGENIC MICEFAILS TO INFLUENCE DIETARY-LIPID ABSORPTION OR FEEDING-BEHAVIOR

Two transgenic mouse lines, expressing low or high amounts of human ap o A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholester ol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carrie d exclusively in chylomicrons and their remnants, was catabolized norm ally. When an intragastric vitamin E bolus is given to the HuAIVTg mic e, the initial absorption and appearance in triglyceride-rich lipoprot eins was similar to that observed in normal mice. However, elevated am ounts of vitamin E were subsequently observed in the VLDL of the HuAIV Tg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high exp ressor mice. Serum total cholesterol was not elevated, but the distrib ution was altered in the HuAIVTg mice; VLDL-C was increased at the exp ense of HDL-C. Kinetic studies suggested a delayed clearance of VLDL i n HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, bu t no effect on feeding behavior or weight gain was observed in these H uAIVTg mice. In summary, our studies with HuAIVTg mice show that addit ional apo A-IV does not effect intestinal absorption of fat and fat-so luble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.