Scientists at McGill University have identified a molecular “on switch” in brown fat that activates a powerful, previously unexplained calorie-burning system, a discovery reported in Nature that could eventually inform treatments for metabolic and bone diseases. The team found that glycerol — a molecule released when fat is broken down in response to cold — binds to an enzyme called TNAP and triggers an alternate heat-generating pathway in mice known as the futile creatine cycle.
Brown fat, unlike white fat which stores energy, burns calories to produce heat. For years researchers thought heat production relied on a single pathway, but a second pathway operating alongside the classic system had been observed without a known activator. Lawrence Kazak and colleagues at McGill’s Rosalind and Morris Goodman Cancer Institute have now identified that activator: glycerol binding to TNAP in a specific site the researchers call the “glycerol pocket.”
Working with structural biologist Alba Guarne, the team showed that glycerol’s interaction with TNAP switches on the alternative heat-producing mechanism. “This is the first time we’ve identified how an alternative heat-producing pathway is activated, independent of the classic system,” said Kazak, Associate Professor in the Department of Biochemistry and Canada Research Chair in Adipocyte Biology. He added that the finding “opens the door to understanding how multiple energy-burning systems work together to keep the body warm at the just-right temperature.”
Beyond metabolism, the discovery has immediate implications for bone health because TNAP is already known to be essential for calcification — the process that builds and maintains strong bone. Mutations that lower TNAP activity cause hypophosphatasia, a rare disorder sometimes called “soft bones,” which can lead to fractures, chronic pain and skeletal abnormalities. The source notes higher prevalence of certain inherited mutations in regions of Canada, including Quebec and Manitoba.
By studying TNAP mutations in the laboratory, the researchers found the same glycerol-activated switch that boosts energy burning in brown fat also affects cells responsible for bone mineralisation and hardening. The work builds on earlier research by McGill co-author Marc McKee and Jose‑Luis Millan, whose prior efforts helped produce a first-in-class enzyme replacement therapy for hypophosphatasia patients with defective TNAP enzymes. “This finding opens the door to a new kind of treatment, where increasing the activity of the TNAP enzyme through its glycerol pocket by natural or synthetic bioactive compounds could potentially boost the beneficial actions of the enzyme in patients, to help restore deficient bone mineralisation to healthy levels,” McKee said.
The study points to the glycerol pocket on TNAP as a potential target for future drugs or bioactive compounds, though the findings to date come from animal and laboratory experiments and will require further research before clinical application.
Original Source: https://theshillongtimes.com/2026/05/14/scientists-find-hidden-molecular-switch-that-strengthen-bones/
Category: Features
Tags:
Publish Date: 2026-05-14 03:20:00
