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.
Highlights
Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion
In search of genes that are potentially involved in FA transport, any potentially involved in FA efflux, we examined the mRNA expression levels of 22 membrane transport proteins from the ABC transporter family and 33 from the solute carrier (SLC) family, which at the time of study did not have a known ligand, in the adipose tissue of patients post bariatric surgery at this critical time
We analyzed the mRNA expression of the six plasma membrane proteins in the SLC family that showed substantial basal expression levels and more than 1.5-fold increase after bariatric surgery in liver and various adipose depots in mice
Summary
Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. In addition to the bidirectional flip-flop model for transporting FAs across the plasma membrane, studies have demonstrated the importance of specific LCFA transport systems in metabolically active tissues, such as intestine, heart, adipose tissue, and the liver [8]. This transport appears to involve membrane proteins that can mediate FA uptake via a rapid, saturable, substrate-specific, and hormonally related mechanism. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with the contents of this article
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