Research

Energy balance

High-intensity or chronic exercise induces nuclear translocation of Transcription Factor EB (TFEB) in skeletal muscle, which independently regulates glucose homeostasis, mitochondrial biogenesis, and metabolic flexibility without requiring PGC1α.

To maximize metabolic flexibility and mitochondrial health, your exercise routine must be intense enough or chronic enough to trigger specific cellular signals. Mild activity may not be sufficient to activate TFEB, a key regulator of glucose and fat metabolism. Focus on progressive, high-intensity training to ensure your muscles adapt efficiently.

GoodSupportsHIGH confidence
Here we show that the calcineurin-TFEB axis plays a major role in the metabolic adaptations that occur during physical exercise. By using gain- and loss-of-function approaches, we show that TFEB regulates mitochondrial biogenesis and glucose uptake independently of PGC1a.
Gelsomina Mansueto et al. · Cell Metabolism · 2016

Why this rating

High-quality mechanistic evidence using multiple mouse models (KO, overexpression, conditional) and human-relevant pathways, though translated from murine models.

Source

Transcription Factor EB Controls Metabolic Flexibility during Exercise

Gelsomina Mansueto et al. · Cell Metabolism · 2016

DOI 10.1016/j.cmet.2016.11.003

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DOI resolved against Crossref · corpus check 2026-06-10

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