title: Evidence for protein-mediated fatty acid efflux by adipocytes.
abstract: OBJECTIVE
  The hormonally controlled mobilization and release of fatty acids from adipocytes into the circulation is an important physiological process required for energy homeostasis. While uptake of fatty acids by adipocytes has been suggested to be predominantly protein-mediated, it is unclear whether the efflux of fatty acids also requires membrane proteins.
  
  
  METHODS
  We used fluorescent fatty acid efflux assays and colorimetric assays for free fatty acids and glycerol to identify inhibitors with effects on fatty acid efflux, but not lipolysis, in 3T3-L1 adipocytes. We assessed the effect of these inhibitors on a fibroblast-based cell line expressing fatty acid transport protein 1, hormone-sensitive lipase and perilipin, which presumably lacks adipocyte-specific proteins for fatty acid efflux.
  
  
  RESULTS
  We identified 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) as an inhibitor of fatty acid efflux that did not impair lipolysis or the cellular exit of glycerol but lead to an accumulation of intracellular fatty acids. In contrast, fatty acid efflux by the reconstituted cellular model for fatty acid efflux was responsive to lipolytic stimuli, but insensitive to DIDS inhibition.
  
  
  CONCLUSIONS
  We propose that adipocytes specifically express an as yet unidentified DIDS-sensitive protein that enhances the efflux of fatty acids and therefore may lead to novel treatment approaches for obesity-related disorders characterized by abnormal lipid fluxes and ectopic triglyceride accumulation.
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California at Berkeley, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Henkin
authors.forename: A M
authors.initials: AM
authors.lastname: Ortegon
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.forename: W-J
authors.initials: WJ
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Falcon
authors.forename: F B
authors.initials: FB
authors.lastname: Kraemer
authors.forename: S-J
authors.initials: SJ
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Stahl
mesh_terms: D041721:3T3-L1 Cells; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003124:Colorimetry; D005227:Fatty Acids / Q000378:metabolism*; D005434:Flow Cytometry; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice
chemical_list: D005227:Fatty Acids; D008565:Membrane Proteins; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid