Fatty acid transport across cell membranes Slc43a3 is a regulator of free fatty acid uptake and efflux

Hasbargen, Kathrin (2019): Fatty acid transport across cell membranes Slc43a3 is a regulator of free fatty acid uptake and efflux. Dissertation, LMU München: Medizinische Fakultät

Abstract

Adipocytes take up long chain fatty acids through diffusion and through a low capacity protein mediated transport system on the plasma membrane, whereas fatty acid efflux is considered to occur by diffusion. Although studies have revealed the importance of fatty acid transport proteins (FATPs), long chain acyl coenzyme A synthetases (ACSLs) and fatty acid translocase (FAT, also known as CD36) in fatty acid uptake, other membrane proteins could be involved, and no membrane proteins have been associated with fatty acid efflux. To identify potential membrane proteins that are involved in regulating fatty acid 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. The expression levels of Slc43a3 in various mouse adipose depots and during adipocyte differentiation were explored in C57Bl6J mice and OP9 murine adipocyte cells. The functional significance of Slc43a3 in regulating fatty acid transport was studied using overexpression or silencing of Slc43a3 in differentiated OP9 cells. Slc43a3 is highly expressed in adipose tissue and induced during adipocyte differentiation in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated fatty acid efflux. Interestingly, knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes also increased fatty acid uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased fatty acid uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate fatty acid flux in adipocytes, functioning as a positive regulator of fatty acid efflux and as a negative regulator of fatty acid uptake.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: lipid droplet, adipose metabolism, membrane transporters, fatty acid uptake, fatty acid efflux
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 19. Dezember 2019
• 1. Bericht­erstatter:in: Parhofer, Klaus