Exp Clin Endocrinol Diabetes 2014; 122 - OP4_11
DOI: 10.1055/s-0034-1371986

FGF21 inhibits adiponectin secretion in human adipocytes

L Berti 1, C Lukas 2, M Irmler 2, J Beckers 2, H Staiger 3, HU Häring 2, 3, 4, M Hrabe' de Angelis 2
  • 1Helmholtz Zentrum München, German Research Center for Environmental Health, IEG, Neuherberg, Germany
  • 2Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 3Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
  • 4Universitätsklinikum, Tübingen, Germany

Differentiating murine subcutaneous preadipocytes express and secrete FGF21 which acts in an autocrine way to enhance differentiation and browning. We asked if (i) differentiating human subcutaneous preadipocytes express and release FGF21, (ii) recombinant human FGF21 (rhFGF21) influences the expression of white and brown adipocyte markers and insulin signaling components, and (iii) differences exist in responses to rhFGF21 between cells from insulin-sensitive (IS) and insulin-resistant (IR) donors. Preadipocytes were obtained from 10 IS and 10 IR participants of the TÜF study, matched for gender, age, and body fat. Cells were differentiated in the presence or absence of rhFGF21. RNA, cell lysates, and conditioned media were analyzed. FGF21 expression was very low in preadipocytes and undetectable in differentiated adipocytes, both in the presence or absence of rhFGF21. The FGF21 receptor FGFR1 and its cofactor KLB were well expressed during the whole differentiation period. RhFGF21 significantly decreased KLB expression (p < 0.05). The expression levels of the white adipocyte markers PPARG, ADIPOQ, and LEP increased independently of rhFGF21. By contrast, expression of UCP1, a brown adipocyte marker, was significantly increased by rhFGF21 from undetectable to very low levels (p < 0.01). RhFGF21 did not affect the expression of INSR, IRS1, AKT1/2, or SLC2A4, but significantly increased SLC2A1 (p < 0.05). RhFGF21 significantly reduced adiponectin release by hSUB (p < 0.01) and significantly increased leptin release (in hSUB from IR donors, p < 0.05). Concomitantly, IL-6 expression and release were also significantly increased by rhFGF21 (p < 0.05). No major differences in rhFGF21 effects were seen in cells from IR versus IS donors. Our data show that FGF21 treatment of human adipocytes has outcomes opposite to those of murine cells. FGF21 may exert insulin-desensitizing actions by potently inhibiting adiponectin release, an effect possibly mediated by IL-6.