Scientists Discover Hidden Molecular Switch That Could Strengthen Bones
New Delhi: Scientists at McGill University have discovered a hidden molecular “switch” that activates a powerful calorie-burning system in brown fat, a breakthrough that could pave the way for new treatments for bone diseases and metabolic disorders.
The findings, published in the journal Nature, reveal how glycerol — a molecule released when fat is broken down during cold exposure — activates an enzyme called TNAP, triggering an alternative heat-producing mechanism in brown fat that scientists had struggled to explain for years.
Brown fat, unlike white fat that stores energy, burns calories to generate heat and plays an important role in metabolism and weight regulation. Scientists had long believed that heat production in brown fat relied on a single biological pathway. However, recent studies identified a second mechanism operating alongside the original system, though its activation process remained unclear.
A research team led by Lawrence Kazak at McGill University’s Rosalind and Morris Goodman Cancer Institute identified the molecular trigger behind this alternative system, known as the “futile creatine cycle.”
The researchers found that when the body is exposed to cold temperatures, stored fat breaks down and releases glycerol. Working alongside structural biologist Alba Guarne, the team discovered that glycerol binds to the TNAP enzyme in a specific region called the “glycerol pocket,” activating the alternative heat-producing pathway.
“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.
“That opens the door to understanding how multiple energy-burning systems work together to keep the body warm at the just-right temperature,” he added.
Researchers said the discovery may have significant implications for bone health because TNAP is already known to play a crucial role in bone formation and mineralization.
The TNAP enzyme is essential for calcification, the process responsible for building and maintaining strong bones. Mutations that reduce TNAP activity can lead to hypophosphatasia, a rare genetic disorder often referred to as “soft bones,” which can cause fractures, chronic pain and skeletal abnormalities.
The condition is more common in certain parts of Canada, including Quebec and Manitoba, due to inherited genetic mutations.
During laboratory experiments, scientists discovered that the same molecular switch involved in energy-burning fat cells also directly influences cells responsible for bone mineralization and hardening.
The study builds on earlier research conducted by McGill co-author Marc McKee and co-author Jose-Luis Millan of the Sanford Burnham Prebys Medical Discovery Institute.
Their previous work contributed to the development of a first-in-class enzyme replacement therapy for patients suffering from hypophosphatasia caused by 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, helping restore deficient bone mineralization to healthy levels,” said McKee.
(DD News)
