Figure 1. Muscle-derived FGF21 enhances glucose uptake in skeletal muscle in Cpt1b^m−/− mice.

(A) Serum FGF21 concentration in 4 month old Cpt1b^m−/− and Cpt1b^fl/fl mice fed and fasted overnight (n=7–9 per group). (B) Fgf21 gene expression in muscle tissue such as gastrocnemius (Gastroc), soleus, extensor digitorium longus (EDL), white and red quads (W.Quad and R.Quad), and other tissue such as liver, epididymal and inguinal white adipose tissue (eWAT and iWAT) from 3–5 month old Cpt1b^m−/− and Cpt1b^fl/fl mice (n=5–8). (C) Immunoblot analysis showing Klotho β and Glut1 protein abundance in gastrocnemius muscle from 4 month old Cpt1b^m−/− and Cpt1b^fl/fl mice. GAPDH used as a loading control. Image J software was used for densitometry quantification of the immunoblots. Results shown are representative of three separate experiments (n=3–4 per group). (D) Fgf21 gene expression primary myotubes established from Cpt1b^m−/− and Cpt1b^fl/fl mice. (E) Secreted FGF21 over 24h in culture media from primary myotubes initiated from Cpt1b^m−/− and Cpt1b^fl/fl mice. (F) Basal and insulin-stimulated [³H]-2-deoxyglucose uptake in primary myotubes from Cpt1b^m−/− and Cpt1b^fl/fl mice. (G) Primary myotubes from Cpt1b^m−/− and Cpt1b^fl/fl mice (3–5 months of age) were pre-treated with vehicle (PBS) or rmFGF21 (250 ng/ml, 16h) and then [³H]-2-deoxyglucose uptake was measured. Results shown are representative of four independent experiments. All data are presented as means ± s.e.m., *P < 0.05 and **P < 0.01 between Cpt1b^m−/− and Cpt1b^fl/fl mice, and ^#P < 0.05 between vehicle versus insulin or rmFGF21 treatments.