Hyperpolarization of the cell membrane of mouse hepatocytes by fatty acid oxidation

Abstract The effect of palmitate and metabolizable and nonmetabolizable monosacharides ( d -glucose, d -fructose and 2-deoxy- d -glucose = 2-DG) on the membrane potential (Vm) of mouse hepatocytes was investigated employing a superfused mouse liver slice technique. Palmitate hyperpolarized the liver cell membrane in a concentration dependent manner whereas the monosaccharides tested did not. When mice were fed a fat-rich diet, the hyperpolarisation was greater in comparison to mice fed a low fat diet. The hyperpolarization was reversed by ouabain, an inhibitor of the Na + /K + -ATPase, by the K + -channel blockers tetra-ethyl-ammonium (TEA) and cetiedil and by three inhibitors of fatty acid oxidation (2-bromopalmitate, 2-bromooctanoate and 4-pentenoate). The results suggest that hyperpolarization of the liver cell membrane is due to fatty acid oxidation and that both activation of Na + /K + -ATPase and opening of K + -channels are involved. The implications of these findings with regard to control of food intake by fatty acid oxidation are discussed. The results are consistent with a role of the hepatic membrane potential in control of food intake by fatty acid oxidation.