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Nat Commun. 2014 Jul 7;5:4282. doi: 10.1038/ncomms5282.

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

Author information

1
1] MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China [2].
2
1] MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China [2] Section of Comparative Medicine, Yale University School of Medicine, PO BOX 208016, New Haven, Connecticut 06520-8016, USA [3].
3
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
4
Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China.

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.

PMID:
24999927
DOI:
10.1038/ncomms5282
[Indexed for MEDLINE]
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