Acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, is controlled by SREBP-2 and affects serum cholesterol levels

Mol Genet Metab. 2012 Nov;107(3):553-60. doi: 10.1016/j.ymgme.2012.08.017. Epub 2012 Aug 29.

Abstract

Ketone bodies have been regarded as an energy source that is mainly produced in the liver, and exported to extrahepatic tissues. However, ketone bodies have also been suggested to be used during the lipogenesis by the ketone body-utilizing enzyme, acetoacetyl-CoA synthetase (AACS). To elucidate the physiological role of AACS in the liver, we investigated the mechanism of transcription of the AACS gene and performed knockdown experiments. We showed that SREBP-2 regulates the expression of AACS and that knockdown of AACS in vivo, by the hydrodynamics method, resulted in the reduction of total blood cholesterol. These results suggest that ketone body metabolism via AACS activity plays an important role in cholesterol homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / blood*
  • Coenzyme A Ligases / antagonists & inhibitors
  • Coenzyme A Ligases / genetics*
  • Coenzyme A Ligases / metabolism
  • Gene Knockdown Techniques
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Hydrodynamics
  • Ketone Bodies / metabolism*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Primary Cell Culture
  • RNA, Messenger / biosynthesis
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 2 / antagonists & inhibitors
  • Sterol Regulatory Element Binding Protein 2 / genetics*
  • Sterol Regulatory Element Binding Protein 2 / metabolism
  • Transcription, Genetic

Substances

  • Ketone Bodies
  • RNA, Messenger
  • RNA, Small Interfering
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 2
  • Cholesterol
  • Coenzyme A Ligases
  • acetoacetyl-CoA synthetase