Apolipoprotein A - IV regulates chylomicron metabolism - mechanism and 1 function 2 3 Alison

42 43 Dietary fat is an important mediator of atherosclerosis and obesity. Despite its 44 importance in mediating metabolic disease, there is still much unknown about 45 dietary fat absorption in the intestine, and especially the detailed biological roles 46 of intestinal apolipoproteins involved in that process. We were specifically 47 interested in determining the physiological role of the intestinal apolipoprotein A48 IV (A-IV) using A-IV knockout (KO) mice. A-IV is stimulated by fat absorption in 49 the intestine, and is secreted on nascent chylomicrons into intestinal lymph. We 50 found that A-IV KO mice had reduced plasma triglyceride (TG) and cholesterol 51 levels, and that this hypolipidemia persisted on a high fat diet. A-IV KO did not 52 cause abnormal intestinal lipid absorption, food intake, or adiposity. Additionally, 53 A-IV KO did not cause abnormal liver TG and cholesterol metabolism, as 54 assessed by measuring hepatic lipid content, lipogenic and cholesterol synthetic 55 gene expression, and in vivo VLDL secretion. Instead, A-IV KO resulted in the 56 secretion of larger chylomicrons from the intestine into the lymph, and those 57 chylomicrons were cleared from the plasma more slowly than WT chylomicrons. 58 This data suggests that A-IV has a previously unknown role in mediating the 59 metabolism of chylomicrons, and therefore may be important in regulating 60 plasma lipid metabolism. 61