Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice.
Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation.
Sáinz
Neira
N
Metabolic Research Laboratory, University of Navarra, Pamplona, Spain.
Rodríguez
Amaia
A
Catalán
Victoria
V
Becerril
Sara
S
Ramírez
Beatriz
B
Gómez-Ambrosi
Javier
J
Frühbeck
Gema
G
D000818:Animals; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000473:pathology; D055435:Myostatin / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors; D020107:Troponin T / Q000096:biosynthesis
D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D020738:Leptin; D055435:Myostatin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D014157:Transcription Factors; D020107:Troponin T; D019938:Cyclin D1