Hypothalamic control of interoceptive hunger

While energy balance is critical to survival, many factors influence food intake beyond caloric need or hunger.Despite this, some neurons that drive feeding in mice are routinely referred to as hunger neurons,whereas others are not. To understand how specific hypothalamic circuits control interoceptive hunger, we trained mice to discriminate fasted from sated periods. We then manipulated three hypothalamic neuronal populations with well-known effects on feeding while mice performed this task. While activation of ARC(AGRP) neurons in sated mice caused mice to report being food-restricted, LHVGAT neuron activation or LHVGLUT2 neuron inhibition did not. In contrast, LHVGAT neuron inhibition or LHVGLUT2 neuron activation in fasted mice attenuated natural hunger, whereas ARC(AGRP) neuron inhibition did not. Each neuronal population evoked distinct effects on food consumption and reward. After satiety-or sickness-induced devaluation, ARC(AGRP) neurons drove calorie-specific feeding, while LHVGAT neurons drove calorie-indiscriminate food intake. Our data support a role for ARC(AGRP) neurons in homeostatic feeding and implicate them in driving a hunger like internal state that directs behavior toward caloric food sources. Moreover, manipulations of LH circuits did not evoke hunger-like effects in sated mice, suggesting that they may govern feeding more related to reward, compulsion, or generalized consumption than to energy balance, but also that these LH circuits can be powerful negative appetite modulators in fasted mice. This study highlights the complexity of hypothalamic feeding regulation and can be used as a framework to characterize how other neuronal circuits affect hunger and identify potential therapeutic targets for eating disorders.

Automated summary

The study reveals the distinct roles of different hypothalamic neuronal populations in regulating internal hunger states and food intake behavior. The manipulation of specific neuronal circuits can evoke varied effects on feeding behaviors, shedding light on potential therapeutic targets for eating disorders.