Feed intake is controlled through a combination of long- and short-term mechanisms. Homeorhetic mechanisms allow adaptation to changes in physiological states in the long term, whereas homeostatic mechanisms are important to maintain physiological equilibrium in the short term. Feed intake is a function of meal size and meal frequency that are controlled by short-term mechanisms over the timeframe of minutes that are modulated by homeorhetic signals to adapt to changes in the physiological state. Control of feed intake by hepatic oxidation likely integrates these mechanisms. Signals from the liver are transmitted to brain feeding centers via vagal afferents and are affected by the hepatic oxidation of fuels. Because fuels oxidized in the liver are derived from both the diet and tissues, the liver is able to integrate long- and short-term controls. Whereas multiple signals are integrated in brain feeding centers to ultimately determine feeding behavior, the liver is likely a primary sensor of energy status.