title: Melissa officinalis essential oil reduces plasma triglycerides in human apolipoprotein E2 transgenic mice by inhibiting sterol regulatory element-binding protein-1c-dependent fatty acid synthesis.
abstract: We investigated the hypolipidemic effects of Melissa officinalis essential oil (MOEO) in human APOE2 transgenic mice and lipid-loaded HepG2 cells. Plasma TG concentrations were significantly less in APOE2 mice orally administered MOEO (12.5 μg/d) for 2 wk than in the vehicle-treated group. Cellular TG and cholesterol concentrations were also significantly decreased in a dose- (400 and 800 mg/L) and time- (12 and 24 h) dependent manner in HepG2 cells stimulated with MOEO compared with controls. Mouse hepatic transcriptome analysis suggested MOEO feeding altered several lipid metabolic pathways, including bile acid and cholesterol synthesis and fatty acid metabolism. In HepG2 cells, the rate of fatty acid oxidation, as assessed using [1-(14)C]palmitate, was unaltered; however, the rate of fatty acid synthesis quantified with [1-(14)C]acetate was significantly reduced by treatment with 400 and 800 mg/L MOEO compared with untreated controls. This reduction was due to the decreased expression of SREBP-1c and its responsive genes in fatty acid synthesis, including FAS, SCD1, and ACC1. Subsequent chromatin immunoprecipitation analysis further demonstrated that the binding of p300/CBP-associated factor, a coactivator of SREBP-1c, and histone H3 lysine 14 acetylation at the FAS, SCD1, and ACC1 promoters were significantly reduced in the livers of APOE2 mice and HepG2 cells treated with MOEO compared with their controls. Additionally, MOEO stimulation in HepG2 cells induced bile acid synthesis and reduced the nuclear form of SREBP-2, a key transcription factor in hepatic cholesterol synthesis. These findings suggest that the intake of phytochemicals with pleasant scent could have beneficial metabolic effects.
authors.affiliation: Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Minh-Hien
authors.initials: MH
authors.lastname: Hoang
authors.forename: Hanna
authors.initials: H
authors.lastname: Byun
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D005227:Fatty Acids / Q000096:biosynthesis; D056945:Hep G2 Cells; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D031334:Melissa / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008517:Phytotherapy; D010938:Plant Oils / Q000008:administration & dosage* / Q000737:chemistry; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D014280:Triglycerides / Q000097:blood*
chemical_list: D053329:Apolipoprotein E2; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D010938:Plant Oils; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D002784:Cholesterol