title: Acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, is controlled by SREBP-2 and affects serum cholesterol levels.
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.
authors.affiliation: Department of Health Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. s-hasegawa@hoshi.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Noda
authors.forename: Akina
authors.initials: A
authors.lastname: Maeda
authors.forename: Masaru
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukui
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood*; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D057446:Hydrodynamics; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051782:Sterol Regulatory Element Binding Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D007657:Ketone Bodies; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D003066:Coenzyme A Ligases; C023747:acetoacetyl-CoA synthetase