Interaction of free fatty acids with human leptin.

Relatively high concentrations of leptin are present in plasma and it is thought to play a major role in lipid homeostasis. Leptin is reported to lower tissue triglyceride content by increasing intracellular oxidation of free fatty acids (FFA). However very little is known regarding the interaction between leptin and plasma FFA. We studied the interaction of FFA with leptin using a direct radiolabelled fatty acid binding assay, a fluorescence assay, electrophoretic mobility and autoradiobinding. All these data indicate that binding of FFA with leptin is reversible and shows a positive co-operativity. The binding of FFA to leptin produces a change in the pI value of the leptin and also increased the electrophoretic mobility of the protein in native polyacrylamide gels. The change in leptin's electrophoretic mobility depends on the chain length and the number of double bonds of the fatty acid, as stearic acid, 18:0, had no effect whereas oleic acid, 18:1n-9, linoleic acid, 18:2n-6, arachidonic acid, 20:4n-6, and docosahexaneoic acid, 22:6n-3, affected leptin's mobility to different degrees. The physiological implication of leptin-FFA interaction is not known, however the interaction may depend on the plasma FFA composition and concentration which are known to vary in different pathological/physiological conditions.