Apolipoprotein AIV (apoAIV) is a lipid-binding protein that is secreted by the small intestine in response to dietary lipid. In vitro evidence suggests that over-expression of apoAIV may protect against atherosclerosis because of changes in reverse cholesterol transport or the oxidation of plasma lipids. However, it is unclear how the knock-out of apoAIV so drastically reduces blood lipids. This important role of apoAIV in lipid metabolism is as yet undefined. The apoAIV KO mouse is a convenient and well- established model for addressing this intriguing question. Based on our preliminary data in apoAIV KO mice, we hypothesize (1) that apoAIV plays an important physiological role in mediating the efficiency with which chylomicrons are taken up by the peripheral tissues and liver;2) that apoAIV acts in the liver to impact the synthesis and/or secretion of TG and cholesterol;and 3) that loss of circulating apoAIV is protective against hyperlipidemia caused by chronic feeding of a high-fat diet.

Public Health Relevance

Apolipoprotein AIV (apoAIV) is a lipid-binding protein that is secreted by the small intestine in response to dietary lipid. The knock-out of apoAIV drastically reduces blood lipid levels. This important role of apoAIV in lipid metabolism is as yet undefined and is the focus of the postdoctoral proposal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK091173-02
Application #
8315289
Study Section
Special Emphasis Panel (ZDK1-GRB-2 (O1))
Program Officer
Podskalny, Judith M,
Project Start
2011-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$52,190
Indirect Cost
Name
University of Cincinnati
Department
Pathology
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Kohan, Alison B; Vandersall, Abbey E; Yang, Qing et al. (2013) The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport. Biochim Biophys Acta 1831:300-5
Kohan, Alison B; Howles, Philip N; Tso, Patrick (2012) Methods for studying rodent intestinal lipoprotein production and metabolism. Curr Protoc Mouse Biol 2:219-230
Wang, Fei; Kohan, Alison B; Kindel, Tammy L et al. (2012) Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion. Proc Natl Acad Sci U S A 109:9641-6
Kohan, Alison B; Wang, Fei; Li, Xiaoming et al. (2012) Apolipoprotein A-IV regulates chylomicron metabolism-mechanism and function. Am J Physiol Gastrointest Liver Physiol 302:G628-36
Kohan, Alison B; Yoder, Stephanie M; Tso, Patrick (2011) Using the lymphatics to study nutrient absorption and the secretion of gastrointestinal hormones. Physiol Behav 105:82-8