Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPAC(Nts) neurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPAC(Nts) neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPAC(Nts) neurons recapitulates these effects, reduces preference for sweet, non-caloric tastants and, furthermore, enhances locomotion and energy expenditure; as a result, mice display long-term weight loss and improved metabolic health and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity.

Automated summary

Obesity is a global pandemic that is associated with many life-threatening diseases. Research shows that neurotensin-expressing neurons in mice play a role in encoding dietary preference for high-energy foods. Activating these neurons promotes obesogenic behaviors, while inhibiting them reduces feeding and hedonic eating. Long-term inactivation leads to weight loss, improved metabolic health, and protection against obesity.