Thalamic opioids from POMC satiety neurons switch on sugar appetite.

Summary

In mice, hypothalamic POMC satiety neurons paradoxically promote sugar appetite via a projection to the paraventricular thalamus that inhibits postsynaptic neurons through mu-opioid receptors. The circuit is preferentially engaged during sugar consumption in sated states, and its inhibition reduces high-sugar intake.

Key Findings

• POMC neurons simultaneously promote satiety and activate sugar appetite.
• A POMC→paraventricular thalamus projection inhibits postsynaptic neurons via mu-opioid receptor signaling.
• The thalamic opioid circuit is strongly engaged during sugar consumption in sated states.
• Inhibiting the circuit reduces high-sugar diet intake in sated mice.

Clinical Implications

While preclinical, mu-opioid signaling in paraventricular thalamus downstream of POMC neurons emerges as a candidate target to curb sugar overconsumption without broadly suppressing appetite. It informs design of neuromodulatory or pharmacologic strategies to reduce high-sugar intake.

Limitations

• Findings are in mice; translational generalizability to humans remains to be established.
• Specificity to sugar rewards versus other palatable nutrients is not fully characterized in the abstract.

Future Directions

Test pharmacologic modulation of thalamic mu-opioid signaling in models of obesity and in human imaging/neuromodulation studies; delineate nutrient specificity and interactions with other reward circuits.