Cellular transport of nonesterified fatty acids

Transport of nonesterified fatty acids (NEFA) is an important component of whole-body energy metabolism, and derangements in NEFA transport have been linked to several diseases. NEFA are transferred from their sites of production to cells in hepatic and peripheral tissues by mechanisms that are regulated in part by cell status and as determined by the covalent structure of the NEFA species. Major barriers to physical transport are transfer from the hydrophobic surfaces on cell membranes and NEFA-binding proteins, such as albumin, into the surrounding aqueous phase and translocation across a membrane that contains a very hydrophobic interior; this process could be purely diffusive or require specific protein cofactors. Herein evidence is provided suggesting that this step is driven by intracellular metabolism that supports a NEFA gradient across the cell membrane. According to current models of NEFA transfer, the rate-limiting step is likely to be desorption of NEFA from the inner leaflet of the cell membrane or intracellular metabolism; for very long chain NEFA, the former is more likely.