Effects of acute leptin administration on the differences in proton leak rate in liver mitochondria from ob/ob mice compared to lean controls

In this investigation, the effects on proton leak of leptin administration to ob/ob mice was measured for liver mitochondria, We and others have shown that proton leak is approximately 3 times greater in liver mitochondria fr om ob/ob mice compared to lean controls at any given membrane potential. Th e results are consistent with obese mammals having higher lean mass-specifi c metabolic rates compared to lean controls. The increase in proton leak ra te at any given membrane potential cannot be explained by the presence of f ree fatty acids associated with mitochondria isolated from the obese animal s. The difference in proton leak must therefore represent a real difference in inner membrane permeability. Acute leptin (OB protein) administration r estores the liver mitochondrial proton leak rate of ob/ob mice to that of l ean controls. There was no effect on proton leak rate of liver mitochondria from sham-treated ob/ob mice. These novel results indicate a role for lept in, either directly or indirectly, in regulating the efficiency of oxidativ e phosphorylation. (C) 1999 Federation of European Biochemical Societies.