Thermal stress induces glycolytic beige fat formation via a myogenic state

Nature. 2019 Jan;565(7738):180-185. doi: 10.1038/s41586-018-0801-z. Epub 2018 Dec 19.


Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acclimatization
  • Adipose Tissue, Beige / cytology*
  • Adipose Tissue, Beige / metabolism*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / metabolism
  • Animals
  • Cell Differentiation
  • Cell Survival
  • Cold Temperature*
  • Cold-Shock Response*
  • Energy Metabolism
  • GA-Binding Protein Transcription Factor / metabolism
  • Glycolysis*
  • Homeostasis
  • Male
  • Mice
  • Muscle Development*
  • MyoD Protein / metabolism
  • Myoblasts / cytology
  • Receptors, Adrenergic, beta / metabolism


  • GA-Binding Protein Transcription Factor
  • Gabpa protein, mouse
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Receptors, Adrenergic, beta