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ABCG5/G8 deficiency results in reduced intestinal cholesterol and fatty acid transport
Author(s) -
Zhang Linda Shuo,
Kohan Alison B,
Tso Patrick
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.242.4
Subject(s) - lymph , cholesterol , medicine , endocrinology , chemistry , abca1 , fatty acid , biochemistry , biology , transporter , pathology , gene
Adenosine triphosphate‐binding cassette (ABC) half transporters G5 and G8 are critical in protecting the body from the accumulation of dietary phytosterols, which is associated with an elevated risk of coronary heart disease. Expressed in the liver and intestines, they are proposed to promote phytosterol excretion and to limit phytosterol absorption. However, the role of G5/G8 in cholesterol and fatty acid (FA) absorption is unclear. The aim of this study was to investigate the effects of G5/G8 deficiency on intestinal lipid transport in chow‐fed mice. We employed the conscious lymph fistula model to examine radiolabeled dietary cholesterol and FA transport into the lymph using wild‐type (WT) and G5/G8 knockout (KO) mice. Since it has been thought that G5/G8 promote sterol excretion, we were surprised to find that G5/G8 KO mice displayed a ~53% reduction in dietary cholesterol transport into the lymph compared to WT controls. In addition, G5/G8 KO mice also displayed a ~45% reduction in FA transport into the lymph. This reduction in cholesterol and FA transport was also accompanied by an accumulation of cholesterol and FAs in the intestinal lumen, suggesting that the loss of G5/G8 inhibit transport across the enterocyte. We conclude that G5/G8 deficiency results in reduced intestinal cholesterol and FA absorption in mice, and therefore may play a previously unknown role in intestinal lipid absorption. Grant Funding Source : University of Cincinnati