Fatty acid transport and transporters in muscle are critically regulated by Akt2

- Akt2 mediates insulin-induced CD36 and FATP1 translocation, similarly to that of GLUT4.
- Akt2 mediates contraction-induced translocation of CD36 and FATP1, but not GLUT4.
- Akt2 mediates intracellular retention of FABPpm and FATP1 in non-stimulated muscle.

Muscle contains various fatty acid transporters (CD36, FABPpm, FATP1, FATP4). Physiological stimuli (insulin, contraction) induce the translocation of all four transporters to the sarcolemma to enhance fatty acid uptake similarly to glucose uptake stimulation via glucose transporter-4 (GLUT4) translocation. Akt2 mediates insulin-induced, but not contraction-induced, GLUT4 translocation, but its role in muscle fatty acid transporter translocation is unknown. In muscle from Akt2-knockout mice, we observed that Akt2 is critically involved in both insulin-induced and contraction-induced fatty acid transport and translocation of fatty acid translocase/CD36 (CD36) and FATP1, but not of translocation of fatty acid-binding protein (FABPpm) and FATP4. Instead, Akt2 mediates intracellular retention of both latter transporters. Collectively, our observations reveal novel complexities in signaling mechanisms regulating the translocation of fatty acid transporters in muscle.