Slc43a3 is a regulator of free fatty acid flux1

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known fu...

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Main Authors: Kathrin B. Hasbargen, Wen-Jun Shen, Yiqiang Zhang, Xiaoming Hou, Wei Wang, Qui Shuo, David A. Bernlohr, Salman Azhar, Fredric B. Kraemer
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520436223
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author Kathrin B. Hasbargen
Wen-Jun Shen
Yiqiang Zhang
Xiaoming Hou
Wei Wang
Qui Shuo
David A. Bernlohr
Salman Azhar
Fredric B. Kraemer
author_facet Kathrin B. Hasbargen
Wen-Jun Shen
Yiqiang Zhang
Xiaoming Hou
Wei Wang
Qui Shuo
David A. Bernlohr
Salman Azhar
Fredric B. Kraemer
author_sort Kathrin B. Hasbargen
collection DOAJ
description Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.
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spelling doaj.art-adee7867d43c4ae8b513887121686c5d2022-12-21T21:48:41ZengElsevierJournal of Lipid Research0022-22752020-05-01615734745Slc43a3 is a regulator of free fatty acid flux1Kathrin B. Hasbargen0Wen-Jun Shen1Yiqiang Zhang2Xiaoming Hou3Wei Wang4Qui Shuo5David A. Bernlohr6Salman Azhar7Fredric B. Kraemer8Division of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Department of Biochemistry,Changzhi Medical College, ShanXi, ChinaDivision of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CADivision of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Department of Biochemistry,Changzhi Medical College, ShanXi, ChinaDivision of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CADivision of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Department of Endocrinology,Peking University First Hospital, Beijing, ChinaVeterans Affairs Palo Alto Health Care System, Palo Alto, CADepartment of Biochemistry, Molecular Biology, and Biophysics,University of Minnesota, Minneapolis, MNDivision of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CATo whom correspondence should be addressed; Division of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Stanford Diabetes Research Center, Stanford, CA; To whom correspondence should be addressedAdipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.http://www.sciencedirect.com/science/article/pii/S0022227520436223lipid dropletadipose metabolismmembrane transportersfatty acid uptakefatty acid effluxsolute carrier family 43 member 3
spellingShingle Kathrin B. Hasbargen
Wen-Jun Shen
Yiqiang Zhang
Xiaoming Hou
Wei Wang
Qui Shuo
David A. Bernlohr
Salman Azhar
Fredric B. Kraemer
Slc43a3 is a regulator of free fatty acid flux1
Journal of Lipid Research
lipid droplet
adipose metabolism
membrane transporters
fatty acid uptake
fatty acid efflux
solute carrier family 43 member 3
title Slc43a3 is a regulator of free fatty acid flux1
title_full Slc43a3 is a regulator of free fatty acid flux1
title_fullStr Slc43a3 is a regulator of free fatty acid flux1
title_full_unstemmed Slc43a3 is a regulator of free fatty acid flux1
title_short Slc43a3 is a regulator of free fatty acid flux1
title_sort slc43a3 is a regulator of free fatty acid flux1
topic lipid droplet
adipose metabolism
membrane transporters
fatty acid uptake
fatty acid efflux
solute carrier family 43 member 3
url http://www.sciencedirect.com/science/article/pii/S0022227520436223
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