New Insights into Hypothalamic Neurons Regulating Energy Expenditure

Researchers from the Chinese Academy of Sciences have uncovered a novel population of hypothalamic neurons that play a crucial role in controlling energy expenditure, a key factor in maintaining energy balance and managing obesity. Published in the journal Neuron on September 17, 2025, their study highlights the importance of Crabp1-expressing GABAergic neurons within the arcuate nucleus (ARC) of the hypothalamus.

Traditionally, the ARC has been studied for its two primary neuronal groups, POMC and AgRP neurons, which regulate food intake and energy use. However, these findings shed light on a previously underexplored cell type—Crabp1 neurons—which exhibit unique molecular characteristics, including pathways linked to cell adhesion, retinoic acid metabolism, and neurotransmitter activity.

Functionally, Crabp1 neurons are vital for maintaining energy expenditure. Silencing these neurons leads to decreased physical activity, lowered core body temperature, impaired brown fat thermogenesis, and consequently, weight gain. Conversely, activation through chemogenetic or optogenetic methods boosts locomotion, enhances thermogenesis, and prevents obesity caused by high-fat diets.

Further circuit analysis revealed that Crabp1 neurons send projections to multiple hypothalamic areas such as the paraventricular nucleus and dorsomedial hypothalamus, coordinating various aspects of energy expenditure. Environmental and behavioral factors also influence their activity; cold exposure and physical exercise activate Crabp1 neurons to promote thermogenesis, while light pollution suppresses their activity, linking lifestyle factors to metabolic health.

This research proposes a new "mirror-imbalance" model of energy regulation, contrasting with the traditional "seesaw" model centered solely on POMC and AgRP neurons. Understanding the molecular and circuit dynamics of Crabp1 neurons opens potential avenues for therapeutic strategies targeting metabolic disorders like obesity.

Source: https://medicalxpress.com/news/2025-09-scientists-neural-basis-energy-expenditure.html