Hyperpolarization of the liver cell membrane by palmitate as affected by glucose and lactate: implications for control of feeding.
Since the membrane potential of liver cells being in contact with vagal afferents has been proposed to represent a major signal in metabolic control of food intake, we investigated the effect of palmitate, glucose and lactate on the membrane potential of hepatocytes with microelectrodes using superfused mouse liver slices. The mice used for the experiments were fed a fat-enriched diet (18% fat). Palmitate (0.5 mM) hyperpolarized the membrane of hepatocytes by 3-4 mV, and this hyperpolarization was not affected by 5-10 mM glucose and 0.5-1 mM lactate. Glucose alone did not influence the potential, even when mice fed a high carbohydrate diet were employed. At lactate concentrations > or = 2 mM the palmitate induced hyperpolarization was eliminated and 5 mM lactate or pyruvate alone hyperpolarized the liver cell membrane. Similar to the palmitate induced hyperpolarization, the lactate induced hyperpolarization was prevented by the K-channel blocker TEA, suggesting that activation of K channels is involved in the hyperpolarization. The results show that physiological concentrations of glucose and lactate do not affect the hyperpolarization of the liver cell membrane due to fatty acid oxidation. The implications of these findings with regard to control of food intake by fatty acid oxidation and lactate metabolism are discussed. The observations are consistent with a signal function of the hepatic membrane potential in physiological control of food intake by fatty acid oxidation. Hepatic lactate metabolism at supraphysiological lactate concentrations may also produce a satiety signal coded by the hepatic membrane potential.
Rossi
R
R
Institut für Veterinär-Physiologie, Zürich, Switzerland.
Scharrer
E
E
D000818:Animals; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007773:Lactates / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010168:Palmitates / Q000494:pharmacology*
D007773:Lactates; D010168:Palmitates; D005947:Glucose