ENPP1 buffers extracellular cGAMP in brown adipose tissue to limit insulin resistance.
- Open access
ENPP1 prevents extracellular cGAMP accumulation in brown adipose tissue, reducing insulin resistance and obesity in high-fat diet conditions.
- Why it matters: Understanding how ENPP1 regulates extracellular cGAMP is crucial because its dysfunction contributes to metabolic diseases like obesity and diabetes, yet the mechanisms remain unclear.
- What they did: The study used a cGAMP-hydrolysis-deficient mouse model (Enpp1 H362A) and identified brown adipose tissue as a key site where extracellular cGAMP builds up, impairing insulin-stimulated glucose uptake through the STING pathway.
- The result: Findings reveal that impaired cGAMP clearance promotes inflammation and metabolic dysfunction, highlighting ENPP1 as a critical immunometabolic checkpoint that supports metabolic health.