Glycerol Switch on TNAP Activates Brown Fat Heat Cycle, Linking to Bone Mineralization

Overview

• McGill-led researchers report in Nature that glycerol binds a defined pocket on the enzyme TNAP to turn on the futile creatine heat‑producing pathway in mice brown fat.
• Cold triggers fat breakdown that releases glycerol, which then binds TNAP in this glycerol pocket to switch on energy burning.
• Lab tests show the same TNAP activation directly affects cells that harden bone, tying brown fat thermogenesis to skeletal mineralization.
• The team has identified dozens of small‑molecule candidates to enhance TNAP through this pocket for bone mineralization disorders, though the work remains experimental and untested in humans.
• TNAP is essential for bone calcification and loss‑of‑function causes hypophosphatasia, and this study builds on prior enzyme‑replacement advances through a collaboration spanning Canada, the UK, and the US.