Hepatic control of feeding: effect of glucose, fructose, and mannitol infusion

Plasma fuels, pancreatic hormones, liver glycogen, and food and water intake were measured immediately before or during the nocturnal feeding period of rats given hepatic portal or jugular infusions of glucose, fructose, and mannitol (0.3 M x 10 ml/2 h). Compared with mock and saline control infusions, hepatic portal glucose, fructose, and mannitol reliably and equally decreased food intake. Jugular fructose and mannitol also decreased food intake when infused before rats ate but not while they ate. Jugular glucose infusion did not affect food intake. Hepatic portal glucose did not reliably elevate systemic plasma glucose or insulin but increased hepatic glycogen content, indicating that most infused glucose was taken up by the liver. In contrast, jugular glucose increased systemic plasma glucose and insulin but did not affect hepatic glycogen. Hepatic portal fructose decreased plasma ketones and increased triglycerides and liver glycogen. Jugular fructose also decreased ketone levels and tended to increase liver glycogen. Mannitol by either route decreased plasma glucose and increased plasma free fatty acids. These results indicate that hepatic portal infusions that produce changes in plasma fuel concentrations within the physiological range decrease food intake. They strongly suggest this is accomplished by a direct action of the infusates on the metabolism of the liver.