Scientists discover hidden fat-burning switch that could strengthen bones
Researchers at McGill University discovered a molecular 'switch' in brown fat that activates an alternative heat-producing pathway via glycerol binding to the enzyme TNAP, which could lead to new treatments for bone diseases like hypophosphatasia. The findings, published in *Nature*, also link this mechanism to bone mineralization and hardening, offering potential therapeutic avenues for conditions causing weak bones.
Scientists at McGill University have identified a previously unknown molecular switch that activates an alternative energy-burning pathway in brown fat. The discovery involves glycerol, a molecule released during fat breakdown in cold conditions, which binds to the enzyme tissue nonspecific alkaline phosphatase (TNAP) and triggers a second heat-producing system called the futile creatine cycle. Led by Lawrence Kazak, the team found that glycerol activates TNAP in a specific region called the glycerol pocket, independent of the classic heat-production pathway. This breakthrough, published in *Nature*, explains how multiple energy-burning systems in brown fat work together to regulate body temperature. The research also highlights TNAP’s role in bone health, as the enzyme is critical for bone calcification. Mutations reducing TNAP activity cause hypophosphatasia, a rare disorder leading to fractures, pain, and skeletal deformities. The condition is more common in parts of Canada, including Quebec and Manitoba, due to inherited genetic factors. By studying TNAP mutations, the researchers confirmed that the same molecular switch affecting brown fat also influences bone mineralization. Their work builds on earlier research by McGill’s Marc McKee and José-Luis Millán, which led to an enzyme replacement therapy for hypophosphatasia patients with defective TNAP. The discovery suggests potential new treatments by targeting the glycerol pocket to boost TNAP activity, either through natural or synthetic compounds. This could improve bone strength and address metabolic disorders linked to brown fat dysfunction.
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