Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice.
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.
J. Shim, C. Moulson, and E. Newberry contributed equally to this work; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Jien
J
Shim
J. Shim, C. Moulson, and E. Newberry contributed equally to this work; Deceased; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Casey L
CL
Moulson
J. Shim, C. Moulson, and E. Newberry contributed equally to this work; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Elizabeth P
EP
Newberry
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Meei-Hua
MH
Lin
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Yan
Y
Xie
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Susan M
SM
Kennedy
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.
Jeffrey H
JH
Miner
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110. Electronic address: nod@im.wustl.edu.
Nicholas O
NO
Davidson
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D050612:Fatty Acid Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D004041:Dietary Fats; D050612:Fatty Acid Transport Proteins; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; C493572:Slc27a4 protein, mouse; D014280:Triglycerides; D002784:Cholesterol