Hypothalamic control of interoceptive hunger.

Area of Science:

• Neuroscience
• Physiology
• Behavioral Science

Background:

• Energy balance is vital for survival, yet factors beyond caloric need influence food intake.
• Specific hypothalamic neurons are implicated in feeding, but their precise roles in hunger are debated.

Purpose of the Study:

• To elucidate how distinct hypothalamic neuronal populations control interoceptive hunger.
• To differentiate the roles of ARC^AGRP and LH circuits in feeding behavior.

Main Methods:

• Mice were trained to discriminate between fasted and sated states.
• Three hypothalamic neuronal populations (ARC^AGRP, LH^VGAT, LH^VGLUT2) were manipulated during the task.

Main Results:

• ARC^AGRP neuron activation induced a hunger state in sated mice; inhibition did not reduce hunger in fasted mice.
• LH^VGAT and LH^VGLUT2 manipulations modulated appetite in fasted mice but not hunger in sated mice.
• ARC^AGRP neurons drove calorie-specific feeding post-devaluation, while LH^VGAT neurons drove calorie-indiscriminate intake.

Conclusions:

• ARC^AGRP neurons are crucial for homeostatic feeding and drive a hunger state for caloric sources.
• LH circuits appear more involved in reward, compulsion, or generalized consumption rather than energy balance.
• This study provides a framework for understanding hypothalamic feeding regulation and identifying therapeutic targets for eating disorders.