title: Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl hesperidin.
abstract: Our previous study has shown that a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), preferentially lowers serum triglyceride (TG) level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein (VLDL) metabolic abnormality. G-Hesperidin has also been found to decrease an elevated serum apolipoprotein B (apo B) level in the hypertriglyceridemic subjects, suggesting a possibility that this compound suppresses excess VLDL secretion in the liver. In the present study, to gain a better understanding of possible mechanisms by which G-hesperidin lowers serum TG, we examined whether this derivative affects apo B secretion from HepG2 human hepatoma cells, a model of hepatic VLDL secretion. As a result, G-hesperidin significantly reduced apo B secretion from the oleate-stimulated HepG2 cells. Furthermore, G-hesperidin significantly suppressed apo B secretion only in the oleate-stimulated cells and failed to act on the cells incubated without oleate. In the oleate-stimulated cells, G-hesperidin significantly decreased cellular cholesteryl ester (CE), although it had no effect on cellular TG or free cholesterol amounts. Moreover, the oleate-stimulated cells had a decrease in cellular apo B amounts by G-hesperidin exposure. These findings indicate that G-hesperidin down-regulates the assembly of apo B-containing lipoproteins via the reduction of CE synthesis augmented with oleate and results in suppressing excess apo B secretion from the cells. This effect is speculated to be associated with the improvement of VLDL metabolic abnormality in hypertriglyceridemic subjects and considered as a mechanism of lowering serum TG.
authors.affiliation: Hayashibara Biochemical Laboratories, Inc., 1-2-3 Shimoishii, Okayama 700-0907, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Miwa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mitsuzumi
authors.forename: Mika
authors.initials: M
authors.lastname: Yamada
authors.forename: Norie
authors.initials: N
authors.lastname: Arai
authors.forename: Fujimi
authors.initials: F
authors.lastname: Tanabe
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Okada
authors.forename: Michio
authors.initials: M
authors.lastname: Kubota
authors.forename: Hiroto
authors.initials: H
authors.lastname: Chaen
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sunayama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kibata
mesh_terms: D000704:Analysis of Variance; D001055:Apolipoproteins B / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008954:Models, Biological; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D002788:Cholesterol Esters; D005960:Glucosides; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C487382:glucosyl hesperidin; D006569:Hesperidin