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

105 Citations (Scopus)

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 2007

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Stearoyl-CoA Desaturase
Metabolism
Lipoproteins
Brain
Triglycerides
Glucose
Liver
VLDL Lipoproteins
Lactic Acid
KATP Channels
Level control
Oleic Acid
Nutrition
Obesity
Chemical activation
Diet
Defects
oleoyl-coenzyme A

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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

Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. / Lam, Tony K T; Gutierrez-Juarez, Roger; Pocai, Alessandro; Bhanot, Sanjay; Tso, Patrick; Schwartz, Gary J.; Rossetti, Luciano.

In: Nature Medicine, Vol. 13, No. 2, 02.2007, p. 171-180.

Research output: Contribution to journalArticle

Lam, TKT, Gutierrez-Juarez, R, Pocai, A, Bhanot, S, Tso, P, Schwartz, GJ & Rossetti, L 2007, 'Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins', Nature Medicine, vol. 13, no. 2, pp. 171-180. https://doi.org/10.1038/nm1540
Lam, Tony K T ; Gutierrez-Juarez, Roger ; Pocai, Alessandro ; Bhanot, Sanjay ; Tso, Patrick ; Schwartz, Gary J. ; Rossetti, Luciano. / Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. In: Nature Medicine. 2007 ; Vol. 13, No. 2. pp. 171-180.
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