Abstract
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.
Highlights
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
Fatp42/2;Ivl-Fatp4tg/1 mice are viable and fertile, with FATP4 expression restricted to keratinocytes within the granular layer of the epidermis [15]
FATP4 was detected in enterocytes from control (Fig. 1A, E), but not Fatp42/2; Ivl-Fatp4tg/1 mice (Fig. 1B, E)
Summary
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. Hirsch, Stahl, and Lodish [10] identified and characterized a family of FA transport proteins (FATPs), each with a tissue specific pattern of expression and a range of possible functions in regard to long-chain FA transport (as reviewed in Ref. 6) One such gene, FATP4 (FA transport protein 4, Slc27a4) is ?60% homologous to the founding member of the family, FATP1, and is abundantly expressed in the small intestine [11], and at lower levels in brain, kidney, liver, and skin [6, 12]. Journal of Lipid Research Volume 50, 2009 491 duced a corresponding, dose-dependent decrease in the uptake of radiolabeled long-chain FA [11] Based on these and other findings, it was proposed that FATP4 was the long sought intestinal FA transport protein
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