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

Thermal stress induces glycolytic beige fat formation via a myogenic state.

Chen Y1,2,3,4, Ikeda K1,2,3, Yoneshiro T1,2,3, Scaramozza A2,5, Tajima K1,2,3, Wang Q1,2,3, Kim K1,2,3, Shinoda K1,2,3,6, Sponton CH1,2,3, Brown Z1,2,3, Brack A2,5, Kajimura S7,8,9.

Author information

1
UCSF Diabetes Center, San Francisco, CA, USA.
2
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA.
3
Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA.
4
Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
5
Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
6
Department of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, New York, NY, USA.
7
UCSF Diabetes Center, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.
8
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.
9
Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.

Abstract

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.

Comment in

PMID:
30568302
PMCID:
PMC6328316
DOI:
10.1038/s41586-018-0801-z
[Indexed for MEDLINE]
Free PMC Article

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