Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins.
Nat Med
; 13(2): 171-80, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17273170
ABSTRACT
Increased production of very low-density lipoprotein (VLDL) is a critical feature of the metabolic syndrome. Here we report that a selective increase in brain glucose lowered circulating triglycerides (TG) through the inhibition of TG-VLDL secretion by the liver. We found that the effect of glucose required its conversion to lactate, leading to activation of ATP-sensitive potassium channels and to decreased hepatic activity of stearoyl-CoA desaturase-1 (SCD1). SCD1 catalyzed the synthesis of oleyl-CoA from stearoyl-CoA. Curtailing the liver activity of SCD1 was sufficient to lower the hepatic levels of oleyl-CoA and to recapitulate the effects of central glucose administration on VLDL secretion. Notably, portal infusion of oleic acid restored hepatic oleyl-CoA to control levels and negated the effects of both central glucose and SCD1 deficiency on TG-VLDL secretion. These central effects of glucose (but not those of lactate) were rapidly lost in diet-induced obesity. These findings indicate that a defect in brain glucose sensing could play a critical role in the etiology of the metabolic syndrome.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Síndrome Metabólico
/
Glucosa
/
Lipoproteínas VLDL
/
Hígado
/
Obesidad
Límite:
Animals
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos