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Papers In Press, published online ahead of print March 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800400-JLR200

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Journal of Lipid Research, Vol. 50, 491-500, March 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice^*,

Jien Shim^1,*, Casey L. Moulson^1,2,*, Elizabeth P. Newberry^1,*, Meei-Hua Lin^*, Yan Xie^*, Susan M. Kennedy^*, Jeffrey H. Miner^*, and Nicholas O. Davidson^3,*,

^* Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110
¹ J. Shim, C. Moulson, and E. Newberry contributed equally to this work.
² Deceased.

^* This work was supported in part by grants from the National Institutes of Health (R01 AR049269) to J.H.M. and (R01 DK056260, R37 HL038180) to N.O.D. and the Washington University Digestive Diseases Research Core Center P30 DK052574 (N.O.D., J.H.M.). C.L.M. was supported by grant K01 DK075811 as well as by pilot and feasibility funding through DK052574.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one table and one figure.

Published, JLR Papers in Press, October 8, 2008.

³ To whom correspondence should be addressed. e-mail: nod{at}im.wustl.edu

FA transport protein 4 (FATP4), one member of a multigene family of FA transporters, was proposed as a major FA transporter in intestinal lipid absorption. Due to the fact that Fatp4^–/– mice die because of a perinatal skin defect, we rescued the skin phenotype using an FATP4 transgene driven by a keratinocyte-specific promoter (Fatp4^–/–;Ivl-Fatp4^tg/+ mice) to elucidate the role of intestinal FATP4 in dietary lipid absorption. Fatp4^–/–;Ivl-Fatp4^tg/+ mice and wild-type littermates displayed indistinguishable food consumption, growth, and weight gain on either low or high fat (Western) diets, with no differences in intestinal triglyceride (TG) absorption or fecal fat losses. Cholesterol absorption and intestinal TG absorption kinetics were indistinguishable between the genotypes, although Western diet fed Fatp4^–/–;Ivl-Fatp4^tg/+ mice showed a significant increase in enterocyte TG and FA content. There was no compensatory upregulation of other FATP family members or any other FA or cholesterol transporters in Fatp4^–/–;Ivl-Fatp4^tg/+ mice. Furthermore, although serum cholesterol levels were lower in Fatp4^–/–;Ivl-Fatp4^tg/+ mice, there was no difference in hepatic VLDL secretion in-vivo or in hepatic lipid content on either a chow or Western diet. Taken together, our studies find no evidence for a physiological role of intestinal FATP4 in dietary lipid absorption in mice.

Supplementary key words dietary • fat • transporter • cholesterol

Abbreviations: FATP, fatty acid transport protein; Ivl, involucrin; TG, triglyceride

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