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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Lam TK,Gutierrez-Juarez R,Pocai A,Bhanot S,Tso P,Schwartz GJ,Rossetti Ldoi
10.1038/nm1540subject
Has Abstractpub_date
2007-02-01 00:00:00pages
171-80issue
2eissn
1078-8956issn
1546-170Xpii
nm1540journal_volume
13pub_type
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