A hypothalamic neuronal population coordinates metabolic adaptations to cold.

Lef1-positive hypothalamic neurons and Kcnk2 modulation coordinate metabolic responses to cold, with Lef1 activation mimicking cold-induced thermogenesis and feeding.

• Why it matters: Understanding how the brain regulates metabolic adaptations to cold is crucial for addressing energy balance and metabolic disorders, yet the neural mechanisms remain poorly defined.
• What they did: Researchers identified cold-responsive neurons in the dorsal posterior periventricular hypothalamus using single-nucleus RNA sequencing, focusing on Lef1 as a marker, and manipulated Kcnk2 activity to assess its role.
• The result: Activation of Lef1 + neurons increased feeding and thermogenesis, while Kcnk2 inhibition amplified cold responses, revealing a neural pathway that links environmental temperature to systemic metabolic regulation.