Evidence for protein-mediated fatty acid efflux by adipocytes

A. H. Henkin, A. M. Ortegon, S. Cho, W. J. Shen, A. Falcon, F. B. Kraemer, S. J. Lee, A. Stahl

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aim: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)562-570
Number of pages9
JournalActa Physiologica
Volume204
Issue number4
DOIs
Publication statusPublished - 2012 Apr

Keywords

  • Adipocyte
  • Fatty acid
  • Lipid metabolism
  • Lipolysis

ASJC Scopus subject areas

  • Physiology

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    Henkin, A. H., Ortegon, A. M., Cho, S., Shen, W. J., Falcon, A., Kraemer, F. B., Lee, S. J., & Stahl, A. (2012). Evidence for protein-mediated fatty acid efflux by adipocytes. Acta Physiologica, 204(4), 562-570. https://doi.org/10.1111/j.1748-1716.2011.02367.x