**4. Concluding remarks**

Homeostatic regulation of feeding is essential for maintenance of total energy balance and whole-body metabolism. NPY/AgRP neurons and POMC neurons in the ARC are the most important neurons in the homeostatic regulation of feeding. New technologies have revealed that the activity of NPY/AgRP neurons changes in response to feeding and fasting. Of note, the activity of these neurons declines rapidly after the onset and before the completion of feeding behavior. Their activity also changes in response to the smell or anticipation of food. The neuronal activity thus appears to be correlated with food values. The evidence suggests that NPY/ AgRP neurons are regulated by anticipatory stimuli related to food reward as well as by energy and nutrient levels in the body.

In addition to the regulation of total calorie intake, that of macronutrient intake appears to be important for maintenance of whole-body metabolism. We found that carbohydrate selection is increased in mice during refeeding after fasting and that this increase is associated with a rapid decrease in plasma ketone body levels. AMPK-regulated CRH neurons in the PVH are necessary and sufficient for this fasting-induced carbohydrate selection. CRH neurons are necessary for stress responses, and social stress can result in carbohydrate craving in humans. AMPKregulated CRH neurons in the PVH may thus contribute to stress-induced carbohydrate craving. Identification of the neural circuits in which AMPK-regulated CRH neurons in the PVH of mice are embedded should shed new light on the physiological and molecular mechanisms responsible for macronutrient selection.
