title: Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion.
abstract: The purpose of the present study was to examine the role of taxifolin, a plant flavonoid, on several aspects involving apolipoprotein B (apoB) secretion and triglyceride (TG) availability in HepG2 cells. Taxifolin was shown by ELISA to markedly reduce apoB secretion under basal and lipid-rich conditions up to 63% at 200 micromol/L. As to the mechanism underlying this effect, we examined whether taxifolin exerted its effect by limiting TG availability in the microsomal lumen essential for lipoprotein assembly. Taxifolin was shown to inhibit microsomal TG synthesis by 37% and its subsequent transfer into the lumen (-26%). The reduction in synthesis was due to a decrease in diacylglycerol acyltransferase (DGAT) activity (-35%). The effect on DGAT activity was found to be non-competitive and non-transcriptional in nature. Both DGAT-1 and DGAT-2 mRNA expression remained essentially unchanged suggesting the point of regulation may be at the post-transcriptional level. Evidence is accumulating that microsomal triglyceride transfer protein (MTP) is also involved in determining the amount of lumenal TG available for lipoprotein assembly and secretion. Taxifolin was shown to inhibit this enzyme by 41%. Whether the reduction in TG accumulation in the microsomal lumen is predominantly due to DGAT and/or MTP activity remains to be addressed. In summary, taxifolin reduced apoB secretion by limiting TG availability via DGAT and MTP activity.
authors.affiliation: Division of Medical Technology, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East-West Road, Biomed C-206, Honolulu, HI 96822, USA.
authors.forename: Adele
authors.initials: A
authors.lastname: Casaschi
authors.forename: Brent K
authors.initials: BK
authors.lastname: Rubio
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Maiyoh
authors.forename: Andre G
authors.initials: AG
authors.lastname: Theriault
mesh_terms: D000217:Acyltransferases / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002352:Carrier Proteins / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase; D004797:Enzyme-Linked Immunosorbent Assay; D044948:Flavonols / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001055:Apolipoproteins B; D002352:Carrier Proteins; D044948:Flavonols; C106092:microsomal triglyceride transfer protein; D011794:Quercetin; C003377:taxifolin; D000217:Acyltransferases; C494881:DGAT1 protein, human; D051048:Diacylglycerol O-Acyltransferase