Exp Clin Endocrinol Diabetes 2013; 121 - OP4_22
DOI: 10.1055/s-0033-1336630

Evidence against a beneficial effect of irisin in humans

S Raschke 1, M Elsen 1, T Romacho 1, K Eckardt 1, J Eckel 1
  • 1German Diabetes Center, Paul-Langerhans-Group, Integrative Physiology, Düsseldorf, Germany

Introduction: Nowadays, brown adipose tissue (AT) has drawn the attention as novel therapeutic target to treat obesity and type 2 diabetes. It generates heat by the activation of mitochondrial uncoupling protein UCP1, protecting against hypothermia and obesity. Expression of PGC1α muscle and exercise induced the expression of the FNDC5 gene, encoding a novel secreted molecule called irisin, which caused browning of subcutaneous AT in mice. The aim of this study was to analyze the potential of irisin in a human model.

Methods: Primary human myotubes and murine C2C12 cells were electrical pulse stimulated (EPS) to induce contraction (1 Hz, 2 ms, 11.5V). Preadipocytes were isolated from subcutaneous AT. During differentiation to mature adipocytes cells were treated with 50 ng/ml BMP7, 200 ng/ml FNDC5 and 60 ng/ml irisin. RNA was isolated for mRNA quantification by RT-PCR.

Results: After 24h EPS of C2C12 myotubes, PGC1α and FNDC5 were significantly increased (1.8fold and 2.1fold, respectively). In primary human skeletal myotubes PGC1α was activated by EPS (1.7fold), while FNDC5 mRNA expression was not changed. Additionally, irisin is 10 times less secreted from human myotubes compared to mice C2C12 myotubes. Most interestingly, in human adipocytes, BMP7 treatment increased adipogenesis measured by PPARγ activation (3.6fold) and enhanced browning of cells measured by UCP-1 expression (6.4 fold), with the strongest effect in CD137 high expressing cells, a novel beige marker. TCF21 mRNA level was significantly diminished by BMP7. FNDC5 and irisin had no significant effect on PPARγ (1.3fold and 0.98fold, respectively) and UCP-1 expression (0.98fold and 0.95fold respectively).

Discussion: Irisin and binding to its receptor might be an interesting strategy to activate the browning of white AT and to combat obesity by increasing energy expenditure. However, our findings raise the question whether the beneficial effect of irisin observed in mice can be transferred to humans.