Division 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, China.
Division of Endocrinology, Gerontology, and Metabolism,Stanford University, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.
J Lipid Res. 2020 May;61(5):734-745. doi: 10.1194/jlr.RA119000294. Epub 2020 Mar 26.
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.
脂肪细胞通过扩散和蛋白介导的运输摄取长链脂肪酸，而脂肪酸的流出被认为是通过扩散发生的。为了鉴定可能参与调节脂肪细胞中脂肪酸通量的膜蛋白，使用分支 DNA 方法在肥胖患者接受减肥手术后的皮下脂肪样本中筛选了 55 种具有未知功能的膜转运蛋白的表达水平。在筛选的 33 种溶质载体 (SLC) 转运蛋白家族成员中，有 14 种成员的表达在减肥手术后发生了显著变化。其中，Slc43a3 在减肥手术后增加了约 2.5 倍。进一步的研究表明，Slc43a3 在小鼠脂肪组织中高度表达，并在原代前体脂肪细胞和 OP9 细胞中诱导脂肪细胞分化。用 siRNA 敲低分化的 OP9 脂肪细胞中的 Slc43a3 减少了基础和福司可林刺激的脂肪酸流出，同时增加了脂肪酸摄取和脂滴积累。相比之下，过表达 Slc43a3 减少了分化的 OP9 细胞中的脂肪酸摄取，并导致脂滴积累减少。因此，Slc43a3 似乎调节脂肪细胞中的脂肪酸通量，作为脂肪酸流出的正调节剂和脂肪酸摄取的负调节剂。
