title: Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.
abstract: Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.
authors.affiliation: a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kang
authors.affiliation: a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
authors.forename: Nipin
authors.initials: N
authors.lastname: S P
authors.affiliation: a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
authors.forename: Pramod
authors.initials: P
authors.lastname: Darvin
authors.affiliation: a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Joung
authors.affiliation: a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
authors.forename: Hyo Joo
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: b Department of Animal Biosystem Science , College of Agriculture and Life Science, Chungnam National University , Daejeon , Korea.
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Do
authors.affiliation: c Department of Animal Biotechnology , Chonbuk National University , Jeonju , Korea.
authors.forename: Kyung Do
authors.initials: KD
authors.lastname: Park
authors.affiliation: d National Institute of Animal Science, RDA , Cheonan , Korea.
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Park
authors.affiliation: d National Institute of Animal Science, RDA , Cheonan , Korea.
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Cho
authors.affiliation: a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007662:Ketosis / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D042682:Angiopoietins; D004224:Diterpenes; D007657:Ketone Bodies; D007783:Lactones; D050799:STAT5 Transcription Factor; C477203:momilactone B; D006904:Hydroxymethylglutaryl-CoA Synthase; D008071:Lipoprotein Lipase
keywords: ANGPTL3-LPL; HMGCS2; STAT5b; ketosis; momilactone B