title: Hesperetin glucuronides induce adipocyte differentiation via activation and expression of peroxisome proliferator-activated receptor-γ.
abstract: In previous reports, hesperidin, a flavonoid glucoside from citrus fruit, is hydrolyzed to hesperetin, an aglycone of hesperidin, and converted to the hesperetin glucuronides (H7-OG and H3'-OG) in vivo and depresses blood glucose levels. But there are no reports on the activity of hesperetin glucuronides. To determine the activity of hesperetin glucuronides, H7-OG and H3'-OG were synthesized and peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity was observed at 250 μM. These glucuronides accelerated the differentiation of 3T3-L1 cells into adipocytes at 10 μM. Furthermore, H7-OG showed additive effects in reporter gene assays and caused noncompetitive reactions in time-resolved fluorescence resonance energy transfer assays with a thiazolidinedione derivative. Our results indicated that hesperetin glucuronides activated PPARγ, accelerated adipocyte differentiation.
authors.affiliation: a Faculty of Science, Department of Life Science , Okayama University of Science , Okayama , Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Gamo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects*; D002522:Chlorocebus aethiops; D002839:Chromans / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D020719:Glucuronides / Q000737:chemistry*; D006569:Hesperidin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D002839:Chromans; D020719:Glucuronides; D047495:PPAR gamma; D045162:Thiazolidinediones; D006569:Hesperidin; D000077288:Troglitazone; C013015:hesperetin
keywords: PPARγ; TR-FRET; glucuronide; hesperidin