title: Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification.
abstract: Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1(+/+) mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In this study, we tested the hypothesis that apoC-I interferes with cellular FFA uptake independent of LPL activity. The cutaneous abnormalities of APOC1(+/+) mice were not affected after transplantation to wild-type mice, indicating that locally produced apoC-I prevents lipid entry into the skin. Subsequent in vitro studies with apoC-I-deficient versus wild-type macrophages revealed that apoC-I reduced the cell association and subsequent esterification of [(3)H]oleic acid by approximately 35% (P < 0.05). We speculated that apoC-I binds FFA extracellularly, thereby preventing cell association of FFA. We showed that apoC-I was indeed able to mediate the binding of oleic acid to otherwise protein-free VLDL-like emulsion particles involving electrostatic interaction. We conclude that apoC-I binds FFA in the circulation, thereby reducing the availability of FFA for uptake by cells. This mechanism can serve as an additional mechanism behind the resistance to obesity and the cutaneous abnormalities of APOC1(+/+) mice.
authors.affiliation: Netherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, Leiden, The Netherlands. m.westerterp@lumc.nl
authors.forename: Marit
authors.initials: M
authors.lastname: Westerterp
authors.forename: Jimmy F P
authors.initials: JF
authors.lastname: Berbée
authors.forename: Dianne J M
authors.initials: DJ
authors.lastname: Delsing
authors.forename: Miek C
authors.initials: MC
authors.lastname: Jong
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Vivian E H
authors.initials: VE
authors.lastname: Dahlmans
authors.forename: Erik H
authors.initials: EH
authors.lastname: Offerman
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
mesh_terms: D000818:Animals; D053302:Apolipoprotein C-I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D062109:Dermatologic Surgical Procedures; D004797:Enzyme-Linked Immunosorbent Assay; D004951:Esterification; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019301:Oleic Acid / Q000493:pharmacokinetics; D010641:Phenotype; D011485:Protein Binding; D012867:Skin / Q000378:metabolism*; D012868:Skin Abnormalities / Q000235:genetics / Q000601:surgery; D016038:Skin Transplantation
chemical_list: D053302:Apolipoprotein C-I; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D019301:Oleic Acid