Apolipoprotein A-IV regulates chylomicron metabolism-mechanism and function.
Dietary fat is an important mediator of atherosclerosis and obesity. Despite its importance in mediating metabolic disease, there is still much unknown about dietary fat absorption in the intestine and especially the detailed biological roles of intestinal apolipoproteins involved in that process. We were specifically interested in determining the physiological role of the intestinal apolipoprotein A-IV (A-IV) using A-IV knockout (KO) mice. A-IV is stimulated by fat absorption in the intestine and is secreted on nascent chylomicrons into intestinal lymph. We found that A-IV KO mice had reduced plasma triglyceride (TG) and cholesterol levels and that this hypolipidemia persisted on a high-fat diet. A-IV KO did not cause abnormal intestinal lipid absorption, food intake, or adiposity. Additionally, A-IV KO did not cause abnormal liver TG and cholesterol metabolism, as assessed by measuring hepatic lipid content, lipogenic and cholesterol synthetic gene expression, and in vivo VLDL secretion. Instead, A-IV KO resulted in the secretion of larger chylomicrons from the intestine into the lymph, and those chylomicrons were cleared from the plasma more slowly than wild-type chylomicrons. These data suggest that A-IV has a previously unknown role in mediating the metabolism of chylomicrons, and therefore may be important in regulating plasma lipid metabolism.
Department of Pathology and Laboratory Medicine, University of Cincinnati, OH 45237, USA. alison.kohan@uc.edu
Alison B
AB
Kohan
Fei
F
Wang
Xiaoming
X
Li
Suzanne
S
Bradshaw
Qing
Q
Yang
Jody L
JL
Caldwell
Tera M
TM
Bullock
Patrick
P
Tso
D050154:Adiposity / Q000235:genetics; D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism*; D001823:Body Composition; D002914:Chylomicrons / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D007408:Intestinal Absorption / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D001054:Apolipoproteins A; D002914:Chylomicrons; D004041:Dietary Fats; D008055:Lipids; C022205:apolipoprotein A-IV