Fatty acid flux in adipocytes: the in's and out's of fat cell lipid trafficking

Abstract

The trafficking of fatty acids into and out of adipocytes is regulated by a complex series of proteins and enzymes and is under control by a variety of hormonal and metabolic factors. The biochemical basis of fatty acid influx, despite its widespread appreciation, remains enigmatic with regard to the biophysical and biochemical properties that facilitate long-chain fatty acid uptake. Fatty acid efflux is initiated by hormonally controlled lipolysis of the droplet stores and produces fatty acids that must transit from their site of production to the plasma membrane and subsequently out of the cells. This review will focus on the "in's and out's" of fatty acid trafficking and summarize the current concepts in the field.

Figure 1

Schematic representation of free fatty acid (FFA) influx mediated by binding to CD36 in caveolin-1-FABP_pm rich microdomains. In one possible scenario, FFA diffuse laterally in the plasma membrane and flip flop across to the inner leaflet where they are enzymatically esterified by FATP1 in an ATP and CoA dependent manner.

Figure 2

Diagrammatic representation of regulated lipolysis. In this scheme, protein kinase A (PKA) dependent phosphorylation of hormone sensitive lipase leads to its translocation from the cytosol to the surface of the lipid droplet. Concurrently, PKA dependent phosphorylation of perilipin A leads to its degradation and loss from the droplet surface enabling assembly of a functional lipolysis complex. Such an activated complex facilitates complete hydrolysis of TAG to glycerol and FFA.