RGD Reference Report - Overexpressed FATP1, ACSVL4/FATP4 and ACSL1 increase the cellular fatty acid uptake of 3T3-L1 adipocytes but are localized on intracellular membranes.

General

Overexpressed FATP1, ACSVL4/FATP4 and ACSL1 increase the cellular fatty acid uptake of 3T3-L1 adipocytes but are localized on intracellular membranes.
Authors:	Zhan, Tianzuo Poppelreuther, Margarete Ehehalt, Robert Füllekrug, Joachim
Citation:	Zhan T, etal., PLoS One. 2012;7(9):e45087. doi: 10.1371/journal.pone.0045087. Epub 2012 Sep 14.
RGD ID:	39458021
Pubmed:	PMID:23024797 (View Abstract at PubMed)
PMCID:	PMC3443241 (View Article at PubMed Central)
DOI:	DOI:10.1371/journal.pone.0045087 (Journal Full-text)
Long chain acyl-CoA synthetases are essential enzymes of lipid metabolism, and have also been implicated in the cellular uptake of fatty acids. It is controversial if some or all of these enzymes have an additional function as fatty acid transporters at the plasma membrane. The most abundant acyl-CoA synthetases in adipocytes are FATP1, ACSVL4/FATP4 and ACSL1. Previous studies have suggested that they increase fatty acid uptake by direct transport across the plasma membrane. Here, we used a gain-of-function approach and established FATP1, ACSVL4/FATP4 and ACSL1 stably expressing 3T3-L1 adipocytes by retroviral transduction. All overexpressing cell lines showed increased acyl-CoA synthetase activity and fatty acid uptake. FATP1 and ACSVL4/FATP4 localized to the endoplasmic reticulum by confocal microscopy and subcellular fractionation whereas ACSL1 was found on mitochondria. Insulin increased fatty acid uptake but without changing the localization of FATP1 or ACSVL4/FATP4. We conclude that overexpressed acyl-CoA synthetases are able to facilitate fatty acid uptake in 3T3-L1 adipocytes. The intracellular localization of FATP1, ACSVL4/FATP4 and ACSL1 indicates that this is an indirect effect. We suggest that metabolic trapping is the mechanism behind the influence of acyl-CoA synthetases on cellular fatty acid uptake.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
long-chain fatty acid import into cell	involved_in	IMP		39458021	PMID:23024797	ARUK-UCL

Cellular Component

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
mitochondrion	located_in	IMP		39458021	PMID:23024797	ARUK-UCL

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
oleoyl-CoA ligase activity	enables	IMP		39458021	PMID:23024797	ARUK-UCL

Objects Annotated

Genes (Rattus norvegicus)

Acsl1 (acyl-CoA synthetase long-chain family member 1)

Additional Information

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Overexpressed FATP1, ACSVL4/FATP4 and ACSL1 increase the cellular fatty acid uptake of 3T3-L1 adipocytes but are localized on intracellular membranes.