An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice.
Cell Metab
; 17(5): 790-7, 2013 May 07.
Article
em En
| MEDLINE
| ID: mdl-23663742
ABSTRACT
FGF21, a member of the fibroblast growth factor (FGF) superfamily, has recently emerged as a regulator of metabolism and energy utilization. However, the exact mechanism(s) whereby FGF21 mediates its actions have not been elucidated. There is considerable evidence that insulin resistance may arise from aberrant accumulation of intracellular lipids in insulin-responsive tissues due to lipotoxicity. In particular, the sphingolipid ceramide has been implicated in this process. Here, we show that FGF21 rapidly and robustly stimulates adiponectin secretion in rodents while diminishing accumulation of ceramides in obese animals. Importantly, adiponectin-knockout mice are refractory to changes in energy expenditure and ceramide-lowering effects evoked by FGF21 administration. Moreover, FGF21 lowers blood glucose levels and enhances insulin sensitivity in diabetic Lep(ob/ob) mice and diet-induced obese (DIO) mice only when adiponectin is functionally present. Collectively, these data suggest that FGF21 is a potent regulator of adiponectin secretion and that FGF21 critically depends on adiponectin to exert its glycemic and insulin sensitizing effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ceramidas
/
Metabolismo Energético
/
Adiponectina
/
Fatores de Crescimento de Fibroblastos
/
Insulina
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
Idioma:
En
Revista:
Cell Metab
Ano de publicação:
2013
Tipo de documento:
Article