Document Detail


Evidence for protein-mediated fatty acid efflux by adipocytes.
MedLine Citation:
PMID:  21951599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A H Henkin; A M Ortegon; S Cho; W-J Shen; A Falcon; F B Kraemer; S-J Lee; A Stahl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-10-25
Journal Detail:
Title:  Acta physiologica (Oxford, England)     Volume:  204     ISSN:  1748-1716     ISO Abbreviation:  Acta Physiol (Oxf)     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-27     Completed Date:  2012-06-08     Revised Date:  2013-09-23    
Medline Journal Info:
Nlm Unique ID:  101262545     Medline TA:  Acta Physiol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  562-70     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.
Affiliation:
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3-L1 Cells
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
Adipocytes / drug effects,  secretion*
Animals
Colorimetry
Fatty Acids / secretion*
Flow Cytometry
Membrane Proteins / drug effects,  metabolism
Mice
Grant Support
ID/Acronym/Agency:
R01 DK066336/DK/NIDDK NIH HHS; R01 DK066336-09/DK/NIDDK NIH HHS; R01 DK089202/DK/NIDDK NIH HHS; R01 DK089202-02/DK/NIDDK NIH HHS; R01AG028098/AG/NIA NIH HHS; R01DK066336/DK/NIDDK NIH HHS; R56 DK066336/DK/NIDDK NIH HHS; R56 DK066336-07/DK/NIDDK NIH HHS; R56DK066336/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Membrane Proteins; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
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