Slc43a3是游离脂肪酸通量的调节剂。,Journal of Lipid Research

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Slc43a3是游离脂肪酸通量的调节剂。
Journal of Lipid Research ( IF 5.0 ) Pub Date : 2020-03-26 , DOI: 10.1194/jlr.ra119000294
Kathrin B Hasbargen ₁ , Wen-Jun Shen ₂ , Yiqiang Zhang ₁ , Xiaoming Hou ₂ , Wei Wang ₃ , Qui Shuo ₄ , David A Bernlohr ₅ , Salman Azhar ₂ , Fredric B Kraemer ₆

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脂肪细胞通过扩散和蛋白质介导的转运吸收长链FA，而认为FA外排是通过扩散发生的。为了鉴定涉及调节脂肪细胞中FA通量的潜在膜蛋白，在肥胖症患者的减肥皮下脂肪样品中，使用分支DNA方法筛选了55种膜蛋白转运蛋白的表达水平。在筛选的33个溶质载体（SLC）转运蛋白家族成员中，减肥手术前后14个成员的表达显示出明显变化。减肥手术后，其中之一Slc43a3增加了约2.5倍。进一步的研究表明，Slc43a3在鼠类脂肪组织中高度表达，并在原代前脂肪细胞和OP9细胞的脂肪细胞分化过程中被诱导。在分化的OP9脂肪细胞中用siRNA敲除Slc43a3可以减少基础和毛喉素刺激的FA外排，同时也增加FA摄取和脂质滴积累。相反，Slc43a3的过表达减少了分化的OP9细胞中的FA摄取，并导致脂质滴积累减少。因此，Slc43a3似乎调节脂肪细胞中的FA通量，作为FA外排的正调节剂和FA摄取的负调节剂。

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Slc43a3 is a regulator of free fatty acid flux.

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.

更新日期：2020-08-21

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