FATP4 contributes as an enzyme to the insulin mediated fatty acid uptake of C2C12 muscle cells

Abstract

The function of membrane proteins in long chain fatty acid transport is controversial. The acyl‐CoA synthetase FATP4 has been suggested to facilitate fatty acid uptake by its enzymatic activity or by direct transport across the plasma membrane. Here, we investigated the role of FATP4 in C2C12 muscle cells, a model system relevant for fatty acid metabolism. Stable expression of exogenous FATP4 resulted in a twofold higher fatty acyl‐CoA synthetase activity, and uptake of radiolabeled oleate was enhanced similarly. We report for the first time that insulin increases the acyl‐CoA synthetase activity within minutes. This short term regulation offers a novel mechanistic explanation for the concomitantly observed enhanced fatty acid uptake. Confocal microscopy showed that FATP4 was localized in an intracellular ER‐like pattern clearly distinct from the plasma membrane. Neither differentiation into myotubes nor insulin treatment changed the intracellular localization of FATP4. We conclude that FATP4 functions by its intrinsic enzymatic activity. This is in line with the concept that intracellular metabolism plays a significant role in the uptake of fatty acids.