Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats

详细信息    查看全文

• 作者：Michael D. Roberts ; David S. Bayless ; Joseph M. Company ; Nathan T. Jenkins ; Jaume Padilla ; Thomas E. Childs ; Jeffrey S. Martin ; Vincent J. Dalbo ; Frank W. Booth ; R. Scott Rector ; M. Harold Laughlin
• 关键词：FNDC5 ; fibronectin type III domain containing 5 ; OLETF ; Otsuka Long-Evans Tokushima Fatty ; LETO ; Long Evans Tokushima Otsuka ; PGC1¦Á ; Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
• 刊名：Metabolism
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：62
• 期：8
• 页码：1052-1056
• 全文大小：580 K

文摘

Objective

There is debate as to whether fibronectin type III domain containing 5 (FNDC5) and its protein product irisin are therapeutic targets for obesity-associated maladies. Thus, we sought to examine FNDC5 mRNA within skeletal muscle of obese/diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats versus lean/healthy Long Evans Tokushima Otsuka (LETO) rats. We hypothesized that FNDC5 expression would be greater in obese (OLETF) versus lean (LETO) animals.

Materials/Methods

Triceps muscle of 30-32 week old OLETF and LETO rats were assayed for FNDC5 and PGC1¦Á mRNA levels. Body composition and circulating biomarkers of the OLETF and LETO rats were also correlated with skeletal muscle FNDC5 mRNA expression patterns in order to examine potential relationships that may exist.

Results

OLETF rats exhibited twice the amount of triceps FNDC5 mRNA compared to LETO rats (p < 0.01). Significant positive correlations existed between triceps muscle FNDC5 mRNA expression patterns versus fat mass (r = 0.70, p = 0.008), as well as plasma leptin (r = 0.82, p < 0.001). PGC1¦Á mRNA levels were also highly correlated with FNDC5 mRNA (r = 0.85, p < 0.001). In subsequent culture experiments, low and high physiological doses of leptin had no effect on PGC1¦Á mRNA or FNDC5 mRNA levels in C₂C₁₂ myotubes. Paradoxically, circulating irisin concentrations tended to be higher in a second cohort of LETO versus OLETF rats (p = 0.085).

Conclusion

These results reveal a positive association between total body adiposity and skeletal muscle FNDC5 gene expression. Of interest, circulating irisin levels tended to be lower in OLETF rats. Further research is needed to examine whether other adipose tissue-derived factors up-regulate FNDC5 transcription and/or inhibit irisin biosynthesis from FNDC5.