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

Zan Huang, Hai-Bin Ruan, Li Xian, Weiqian Chen, Shujun Jiang, Anying Song, Qinghua Wang, Peiliang Shi, Xingxing Gu and Xiang Gao ()
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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
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

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5282

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