GUSB-enriched sympathetic neurons promote thermogenic recruitment through extracellular matrix remodelling in male mice.

GUSB-enriched sympathetic neurons in male mice secrete GUSB after cold exposure, driving extracellular matrix remodeling that is essential for thermogenic programming, including CS fragment generation.

• Why it matters: The missing piece is how sympathetic neurons directly connect to extracellular matrix remodeling that sustains adipose thermogenic recruitment.
• What they did: Cold exposure activates a β-glucuronidase (GUSB)-enriched sympathetic neuron subpopulation to secrete GUSB, which degrades glycosaminoglycans into bioactive chondroitin sulphate (CS) fragments in adipose tissue. CS then signals via CD97 receptors on adipocytes to potentiate thermogenic activation.
• The result: Human GUSB variants that impair this pathway link sympathetic–ECM crosstalk to obesity, and CS supplementation ameliorates diet-induced obesity in murine models by enhancing thermogenic recruitment.

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