RESUMEN
Endogenous polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm) affect adipocyte differentiation. In this study, we investigated the effect of exogenously supplemented polyamines on mouse adipocyte differentiation and anti-obesity actions in vitro and in vivo. The preadipocyte cell line, 3T3-L1, was cultured with Put, Spd, or Spm, and lipid accumulation in the cells was measured by Oil Red O staining. Lipid accumulation was significantly suppressed by Spm. Suppression of CCAAT/enhancer binding protein α mRNA by Spm suggested that the decreased lipid accumulation was due to delaying the cell differentiation. The body weight and fat of obese mice induced with a high-fat diet were reduced by oral ingestion of Spm. In conclusion, oral supplementation of Spm has the ability to prevent obesity through inhibition of adipocyte differentiation.
Asunto(s)
Fármacos Antiobesidad , Espermina , Células 3T3-L1 , Adipocitos/metabolismo , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Diferenciación Celular , Lípidos/farmacología , Ratones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Poliaminas/metabolismo , Putrescina/metabolismo , ARN Mensajero/metabolismo , Espermidina/metabolismo , Espermina/metabolismo , Espermina/farmacologíaRESUMEN
Osteoclasts are the only bone-resorbing cells in organisms and understanding their differentiation mechanism is crucial for the treatment of osteoporosis. In the present study, we investigated the effect of Thiamet G, an O-GlcNAcase specific inhibitor, on osteoclastogenic differentiation. Thiamet G treatment increased global O-GlcNAcylation in murine RAW264 cells and suppressed receptor activator of nuclear factor-κB ligand (RANKL)-dependent formation in tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells, thereby suppressing the upregulation of osteoclast specific genes. Meanwhile, knockdown of O-linked N-acetylglucosamine (O-GlcNAc) transferase promoted the formation TRAP-positive multinuclear cells. Thiamet G treatment also suppressed RANKL and macrophage colony-stimulating factor (M-CSF) dependent osteoclast formation and bone-resorbing activity in mouse primary bone marrow cells and human peripheral blood mononuclear cells. These results indicate that the promotion of O-GlcNAc modification specifically suppresses osteoclast formation and its activity and suggest that chemicals affecting O-GlcNAc modification might potentially be useful in the prevention or treatment of osteoporosis in future.