Overexpression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in transgenic mice causes hepatic hyperketogenesis

Alfons Valera, Mireia Pelegrin, Guillermina Asins, Cristina Fillat, Jordi Sabater, Anna Pujol, Fausto G. Hegardt, Fatima Bosch

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) is a key enzyme in the ketone body pathway. To determine its role in the regulation of liver ketogenesis, transgenic mice expressing a P-enolpyruvate carboxykinase/HMG-CoA synthase chimeric gene have been obtained. An increase in the concentration of mitochondrial HMG-CoA synthase mRNA was detected in these mice, which was associated with a 3-fold increase in HMG-CoA synthase activity in liver mitochondrial extracts. Transgenic mice were normoglycemic and had normal levels of plasma triglycerides and lower free fatty acids. However, the plasma concentration of ketone bodies was about three times higher in transgenic mice than in control animals. Hepatocytes in primary culture from transgenic mice expressed the chimeric gene in a regulated manner and showed a 3-fold increase in β-hydroxybutyrate and acetoacetate concentrations in the medium. This animal model thus shows that the overexpression of mitochondrial HMG-CoA synthase causes ketone body overproduction, suggesting that this enzyme may be a regulatory step in liver ketogenesis.
Original languageEnglish
Pages (from-to)6267-6270
JournalJournal of Biological Chemistry
Volume269
Issue number9
Publication statusPublished - 4 Mar 1994

Fingerprint Dive into the research topics of 'Overexpression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in transgenic mice causes hepatic hyperketogenesis'. Together they form a unique fingerprint.

  • Cite this

    Valera, A., Pelegrin, M., Asins, G., Fillat, C., Sabater, J., Pujol, A., Hegardt, F. G., & Bosch, F. (1994). Overexpression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in transgenic mice causes hepatic hyperketogenesis. Journal of Biological Chemistry, 269(9), 6267-6270.