Slc43a3 is a regulator of free fatty acid flux

J Lipid Res. 2020 May;61(5):734-745. doi: 10.1194/jlr.RA119000294. Epub 2020 Mar 26.

Abstract

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.

Keywords: adipose metabolism; fatty acid efflux; fatty acid uptake; lipid droplet; membrane transporters; solute carrier family 43 member 3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Amino Acid Transport Systems / deficiency
  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism*
  • Animals
  • Biological Transport
  • Cell Line
  • Cyclic AMP / metabolism
  • Fatty Acids, Nonesterified / metabolism*
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Membrane Transport Proteins / genetics
  • Mice
  • RNA, Messenger / genetics
  • Young Adult

Substances

  • Amino Acid Transport Systems
  • Fatty Acids, Nonesterified
  • Membrane Transport Proteins
  • RNA, Messenger
  • SLC43A3 protein, human
  • Adenosine Triphosphate
  • Cyclic AMP