Efectos de la leptina en el músculo esquelético

  1. Sáinz Amillo, Neira
Supervised by:
  1. Gema Frühbeck Martínez Director
  2. Javier Gómez Ambrosi Co-director

Defence university: Universidad de Navarra

Fecha de defensa: 20 November 2009

Committee:
  1. Carlos Diéguez González Chair
  2. María Angela Burrell Bustos Secretary
  3. F. Javier Salvador Rodríguez Committee member
  4. Mariano Ruiz Gayo Committee member
  5. María M. Malagón Poyato Committee member
Department:
  1. (FM) Endocrinología y Nutrición

Type: Thesis

Teseo: 107450 DIALNET

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.