Is membrane transport of FFA mediated by lipid, protein, or both? An unknown protein mediates free fatty acid transport across the adipocyte plasma membrane.

1548-9213/04 5.00 ©2006 Int. Union Physiol. Sci./Am. Physiol. Soc. tions; they provide a major portion of physiological energy needs (42), are important constituents in the synthesis of complex lipids, and play critical roles in cell signaling (18). Most FFA are obtained from circulating plasma FFA, the levels of which are regulated by the rate at which FFA are generated, predominantly by adipose tissue (43), and the rate at which they are metabolized, predominantly by liver, muscle, and adipose tissue. Regulation of circulating FFA levels is critical because FFA play essential roles in homeostasis; deviations from normal levels reflect pathology and may adversely affect health (5, 6, 23, 31, 33, 34, 37, 40, 44, 45, 55). Although most FFA in circulation are bound to albumin (48, 56), the small fraction of unbound FFA (FFAu) in the aqueous phase mediates physiological activity and is most sensitive to changes in health and disease (5, 49, 66). Moreover, the FFAu, not FFA-albumin complexes, are transported across membranes. In the course of their storage, production, and consumption, FFA must cross the plasma and mitochondrial membranes of many different cells. Because these membranes might be involved in the regulation of FFA trafficking, the mechanism by which FFA are transported across membranes has been an area of considerable interest for over 40 years (57).