Tesis doctoral de Neira Sáinz Amillo
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.
Datos académicos de la tesis doctoral «Efectos de la leptina en el músculo esquelético«
- Título de la tesis: Efectos de la leptina en el músculo esquelético
- Autor: Neira Sáinz Amillo
- Universidad: Navarra
- Fecha de lectura de la tesis: 20/11/2009
Dirección y tribunal
- Director de la tesis
- Gema FrÁ¼hbeck Martínez
- Tribunal
- Presidente del tribunal: Carlos Dieguez gonzalez
- Francisco Javier Salvador rodríguez (vocal)
- María no Ruiz gayo (vocal)
- María del mar Malagon poyato (vocal)
