FATP1 channels exogenous FA into 1,2,3-triacyl-sn-glycerol and down-regulates sphingomyelin and cholesterol metabolism in growing 293 cells

Grant M. Hatch, Anne J. Smith, Fred Y. Xu, Angela M. Hall, David A. Bernlohr

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64 Scopus citations

Abstract

Biosynthesis of lipids was investigated in growing 293 cells stably expressing fatty acid (FA) transport protein 1 (FATP1), a bifunctional polypeptide with FA transport as well as fatty acyl-CoA synthetase activity. In short-term (30 s) incubations, FA uptake was increased in FATP1 expressing cells (C8 cells) compared with the vector (as determined by BODIPY 3823 staining and radioactive FA uptake). In long-term (4 h) incubations, incorporation of [14C]acetate, [3H]oleic acid, or [14C]lignoceric acid into 1,2,3-triacyl-snglycerol (TG) was elevated in C8 cells compared with vector, whereas incorporation of radiolabel into glycerophospholipids was unaltered. The increase in TG biosynthesis correlated with an increase in 1,2-diacyl-sn-glycerol acyltransferase activity in C8 cells compared with vector. In contrast, incorporation of [14C]acetate into sphingomyelin (SM) and cholesterol, and [3H]oleic acid or [14C]lignoceric acid into SM was reduced due to a reduction in de novo biosynthesis of these lipids in C8 cells compared with vector. The results indicate that exogenously supplied FAs, and their subsequently produced acyl-CoAs, are preferentially channeled by an FATP1 linked mechanism into the TG biosynthetic pathway and that such internalized lipids down-regulate de novo SM and cholesterol metabolism in actively growing 293 cells.

Original languageEnglish (US)
Pages (from-to)1380-1389
Number of pages10
JournalJournal of lipid research
Volume43
Issue number9
DOIs
StatePublished - Sep 2002

Keywords

  • CoA synthetase
  • Esterification
  • Fatty acid transport protein 1
  • Transport

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