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The stem cell factor/Kit signalling pathway regulates mitochondrial function and energy expenditure

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Listed:
  • Zan Huang

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Hai-Bin Ruan

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University
    Section of Comparative Medicine, Yale University School of Medicine)

  • Li Xian

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Weiqian Chen

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Shujun Jiang

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Anying Song

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Qinghua Wang

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Peiliang Shi

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

  • Xingxing Gu

    (Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University)

  • Xiang Gao

    (MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University)

Abstract

Cell growth is tightly coupled with mitochondrial biogenesis in order to maintain energy and organelle homeostasis. Receptor tyrosine kinase Kit and its ligand, stem cell factor (SCF), play a critical role in the growth and survival of multiple cell lineages. Here we report that the expression of SCF and Kit in adipose tissues is responsive to food availability and environmental temperature, and is altered in obese mice and human patients. Mice carrying a loss-of-function mutation in Kit develop obesity as a result of decreased energy expenditure. These phenotypes are associated with reduced PGC-1α expression and mitochondrial dysfunction in brown adipose tissue and skeletal muscle. We further demonstrate that SCF/Kit directly promotes Ppargc1a transcription and mitochondrial biogenesis. Blocking Kit signalling in mice decreases PGC-1α expression and thermogenesis, while overexpressing SCF systemically or specifically in brown adipose tissue increases thermogenesis and reduces weight gain. Collectively, these data provide mechanistic insight into the regulation of mitochondrial function by SCF/Kit signalling and lay a foundation for exploring SCF/Kit signalling as a therapeutic target for metabolic diseases.

Suggested Citation

  • Zan Huang & Hai-Bin Ruan & Li Xian & Weiqian Chen & Shujun Jiang & Anying Song & Qinghua Wang & Peiliang Shi & Xingxing Gu & Xiang Gao, 2014. "The stem cell factor/Kit signalling pathway regulates mitochondrial function and energy expenditure," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5282
    DOI: 10.1038/ncomms5282
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    Cited by:

    1. Hyuek Jong Lee & Jueun Lee & Myung Jin Yang & Young-Chan Kim & Seon Pyo Hong & Jung Mo Kim & Geum-Sook Hwang & Gou Young Koh, 2023. "Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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