Effects of oral and parenteral quinine on rats with ventromedial hypothalamic knife-cut obesity.

The addition of quinine to the food reversed the obesity in rats with hypothalamic hyperphagia induced by knife cuts. Similarly, the injection of quinine into rats with hypothalamic knife cuts reduced food intake and body weight but the effects were smaller than those observed when quinine was added to the diet. Urinary quinine excretion was similar by the oral and parenteral routes. The food intake of the knife-cut animals receiving quinine gradually fell to the same level as in the sham-operated animals receiving quinine by either route. The weights of retroperitoneal fat pads were related to the weights of the animals and were reduced in the quinine-treated groups. Plasma insulin concentrations were significantly higher in the knife-cut animals and were reduced toward control levels by quinine treatment. Gluconeogenesis, measured by incorporation of radioactivity from labeled bicarbonate into glucose, was unaffected by treatment with quinine or by knife cuts. Lipogenesis from tritiated water in vivo was not different between treatment groups in the liver or retroperitoneal fat pads. However, in vivo lipogenesis was reduced in knife-cut rats fed ad libitum compared with quinine-treated rats. The response of lipogenesis to insulin in vitro was also not different between treatment groups. These data suggest that a major part of the reduction in food intake in hyperphagic rats eating a quinine-adulterated diet is due to postingestional events.