Obesity and the hepatic control of feeding behavior

Despite its well-established role in the control of food intake, the liver has not been a target for the development of drugs to modulate appetite and treat obesity. This paper provides an overview of the hepatic control of food intake and focuses in particular on how it may play a part in overeating and body weight gain. Signals from the liver that control feeding behavior are triggered in response to changes in liver energy status and are carried to the brain by vagal sensory neurons. Consumption of diets rich in fat and carbohydrate is a major contributing cause of overeating and obesity, and susceptibility to such diet-induced obesity is associated with a reduced capacity for fat oxidation. Inhibition of fatty acid oxidation in the liver stimulates food intake by decreasing liver ATIP production, suggesting that low liver energy status may contribute to diet-induced overeating and obesity. These findings raise the possibility that liver energy production, the mechanisms that transduce changes in hepatic energy status into neural signals or hepatic vagal afferent activity may provide new targets for the development of drugs for appetite control and obesity. (C) 2007 Prous Science. All rights reserved.