Send to

Choose Destination
J Lipid Res. 2015 Aug;56(8):1403-18. doi: 10.1194/jlr.R052753. Epub 2015 Feb 1.

Apolipoprotein A-IV: a protein intimately involved in metabolism.

Author information

Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237.
Department of Nutritional Sciences, University of Connecticut Advanced Technology Laboratory, Storrs, CT 06269.


The purpose of this review is to summarize our current understanding of the physiological roles of apoA-IV in metabolism, and to underscore the potential for apoA-IV to be a focus for new therapies aimed at the treatment of diabetes and obesity-related disorders. ApoA-IV is primarily synthesized by the small intestine, attached to chylomicrons by enterocytes, and secreted into intestinal lymph during fat absorption. In circulation, apoA-IV is associated with HDL and chylomicron remnants, but a large portion is lipoprotein free. Due to its anti-oxidative and anti-inflammatory properties, and because it can mediate reverse-cholesterol transport, proposed functions of circulating apoA-IV have been related to protection from cardiovascular disease. This review, however, focuses primarily on several properties of apoA-IV that impact other metabolic functions related to food intake, obesity, and diabetes. In addition to participating in triglyceride absorption, apoA-IV can act as an acute satiation factor through both peripheral and central routes of action. It also modulates glucose homeostasis through incretin-like effects on insulin secretion, and by moderating hepatic glucose production. While apoA-IV receptors remain to be conclusively identified, the latter modes of action suggest that this protein holds therapeutic promise for treating metabolic disease.


chylomicron; diabetes; glucose tolerance; incretins; intestinal lipid transport; lymph fistula mouse model; obesity

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center