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Publication : Lactate induces FGF21 expression in adipocytes through a p38-MAPK pathway.

First Author  Jeanson Y Year  2016
Journal  Biochem J Volume  473
Issue  6 Pages  685-92
PubMed ID  26769382 Mgi Jnum  J:239503
Mgi Id  MGI:5828993 Doi  10.1042/BJ20150808
Citation  Jeanson Y, et al. (2016) Lactate induces FGF21 expression in adipocytes through a p38-MAPK pathway. Biochem J 473(6):685-92
abstractText  FGF21 (fibroblast growth factor 21), first described as a main fasting-responsive molecule in the liver, has been shown to act as a true metabolic regulator in additional tissues, including muscle and adipose tissues. In the present study, we found that the expression and secretion of FGF21 was very rapidly increased following lactate exposure in adipocytes. Using different pharmacological and knockout mice models, we demonstrated that lactate regulates Fgf21 expression through a NADH/NAD-independent pathway, but requires active p38-MAPK (mitogen activated protein kinase) signalling. We also demonstrated that this effect is not restricted to lactate as additional metabolites including pyruvate and ketone bodies also activated the FGF21 stress response. FGF21 release by adipose cells in response to an excess of intermediate metabolites may represent a physiological mechanism by which the sensing of environmental metabolic conditions results in the release of FGF21 to improve metabolic adaptations.
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