Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins

Tony K.T. Lam, Roger Gutierrez-Juarez, Alessandro Pocai, Sanjay Bhanot, Patrick Tso, Gary J. Schwartz, Luciano Rossetti

Research output: Contribution to journalArticle

107 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalNature Medicine
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins'. Together they form a unique fingerprint.

  • Cite this

    Lam, T. K. T., Gutierrez-Juarez, R., Pocai, A., Bhanot, S., Tso, P., Schwartz, G. J., & Rossetti, L. (2007). Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. Nature Medicine, 13(2), 171-180. https://doi.org/10.1038/nm1540