Stem Cell Factor/Kit Signaling Pathway Regulates Adaptive Thermogenesis In Mice

Stem cell factor (SCF) can bind to its receptor Kit, and activate its receptor tyrosine kinase. Activation of SCF/Kit pathway can mediate cell survival, migration, and proliferation in various cells. Signaling from SCF/Kit is crucial for normal hematopoiesis, pigmentation, fertility in mice. Recent researches show that this pathway is involved in pancreas development, fat metabolism, as well as the differentiation of brown adipocytes.In this study, we found serum SCF was increased in not only obese human, but also a number of obese mice model. And the increased serum SCF is a result of up regulated expression of SCF in BAT. Further investigations showed SCF increased in BAT and soleus when mice were stimulated with high fat diet, recent food intake, and cold environment.We identified a novel kit loss-of-function-mutated mice strain, Wps. These mice were cold intolerant and obese. The phenotypes were resulted from impaired mitochondria in BAT and soleus. Further investigations suggested that down-regulated PGC-1α in these organs respond for these phenotypes.To further investigate whether SCF can directly activate brown adipocyte, we establish a brown adipocyte cell line. Researches on this cell line indicated that the expression of PGC-1α was impaired when cells were treated with kit inhibiter. And to confirm the thermogenesis effect of SCF, wild type mice were injected with SCF-expression lentivirus. Mice injected in BAT resisted from body temperature decrease when they were put in cold. Mean while, mice with lentivirues injected into tail veil increased their body temperature, and decreased their body weight.Taken together, our data indicate a relation between SCF/kit pathway and thermogenesis, and suggest the novel "thermogenesis hormone" function of SCF. In addition to this, we found SCF can regulate the expression of PGC-1a, and further increased mitochondria genesis.