The DMHGABA Neurons Play a Crucial Role in the Regulation of Cold-Induced White Adipose Browning through DMH to LPO Projection.

The browning of white adipose tissue (WAT) can convert energy-storing WAT into energy-dissipating beige adipose tissue to combat obesity and metabolic dysfunction. Cold exposure is a WAT browning-inducing condition in mice. Hypothalamus regulates WAT browning. However, the mechanism of central regulation of WAT browning is still elusive. Here, it is reported that GABAergic neurons in the dorsomedial hypothalamus (DMHGABA neurons) are activated in response to cold exposure. Designer receptors exclusively activated by designer drugs (DREADDs) activation of DMHGABA neurons elicited WAT browning, increased energy expenditure, lowered fat mass weights, and body weight. Conversely, inactivation of DMHGABA neurons showed the opposite effects. Cell type-specific anterograde tracing revealed that DMHGABA neurons projected to the lateral preoptic area (LPO). Chemogenetic and optogenetic functional circuit interrogation demonstrated that the activation of this projection induced WAT browning. Together, it is uncovered that DMHGABA neurons may act as a key neuronal population controlling cold exposure-induced WAT browning. DMHGABA neurons regulate WAT browning through DMH to LPO projection. This study expands the understanding of the central mechanism governing the white adipose browning, as well as the anti-obesity effects of cold therapy.