title: Leptin as a Potential Regulator of FGF21.
abstract: OBJECTIVE
  Fibroblast growth factor 21 (FGF21), a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21.
  
  
  METHODS
  We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site.
  
  
  RESULTS
  We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells.
  
  
  CONCLUSIONS
  New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Asrih
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Poher
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lyautey
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.forename: François R
authors.initials: FR
authors.lastname: Jornayvaz
mesh_terms: D000818:Animals; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors