Efectos de la leptina en el músculo esquelético

Abstract

A reduced skeletal muscle mass has been observed in leptin-deficient ob/ob mice. The aim of the present study was to analyze the effect of leptin on the anabolic and catabolic pathways regulating muscle mass. Ten-week-old male wild type (C57BL/6J) (n=30) and genetically obese ob/ob mice (C57BL/6J) (n=30) were divided in control, leptin-treated and pair-fed groups (n=10 per group). The control wild type (WV), pair-fed wild type (WP), control ob/ob (OV) and pair-fed ob/ob (OP) groups received vehicle (PBS), while leptin-treated wild type (WL) and leptin-treated ob/ob (OL) groups were intraperitoneally administered with leptin (1 mg/kg/d) for 28 days. Muscle mass and fiber size of gastrocnemius, EDL and soleus were significantly lower in OV compared to WV (P<0.001), being significantly increased following leptin administration as compared to OV and OP groups (P<0.001). These effects were associated with an inactivation of the muscle atrophy-related transcription factor FoxO3a (P=0.023), together with a decrease in the protein expression levels of the E3 ubiquitin-ligases MAFbx (P=0.014) in gastrocnemius muscle of wild type and ob/ob mice and of the MuRF1 as compared to OV and OP groups (P<0.05). Protein expression levels of PGC-1¿Ñ, a regulator of muscle fiber type, were lower in ob/ob mice compared to wild type (P=0.01), being significantly increased by leptin administration (P=0.005). Furthermore, myostatin protein, a negative regulator of muscle growth, was reduced in OL compared to both OV (P=0.026) and OP (P=0.015) groups. Leptin administration also activated the positive regulators of cell cycle progression, PCNA (P=0.002) and cyclin D1 (P=0.005), in wild type and ob/ob mice, while it inhibited the negative regulator p27kip1 (P=0.004). In addition, the amount of the slow (P=0.001) and fast (P=0.012) isoforms of the myofibrillar protein troponin T was increased by leptin in wild type and ob/ob mice. The present study provides evidence that leptin treatment increases muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation.