title: A Limonoid Kihadanin B from Immature Citrus unshiu Peels Suppresses Adipogenesis through Repression of the Akt-FOXO1-PPARγ Axis in Adipocytes.
abstract: Citrus limonoids are secondary metabolites and exhibit a variety of biological activities. In this study, we elucidated the suppression of adipogenesis by a Citrus limonoid kihadanin B and determined its molecular mechanism in mouse 3T3-L1 adipocytes. Kihadanin B was purified from the peels of immature Citrus unshiu by HPLC, and its chemical structure was determined by NMR and mass spectrometry. Kihadanin B reduced the lipid accumulation with the reduction of the expression levels of the adipogenic and lipogenic genes, but did not affect lipolysis in adipocytes. Phosphorylation levels of Akt and a forkhead transcriptional factor, FOXO1, a repressor of PPARγ, were lowered by kihadanin B. Furthermore, kihadanin B increased the binding level of FOXO1 to the PPARγ gene promoter in adipocytes. These results indicate that a Citrus limonoid kihadanin B repressed the adipogenesis by decreasing lipid accumulation through the suppression of the Akt-FOXO1-PPARγ axis in 3T3-L1 adipocytes.
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Baba
authors.affiliation: Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Ko
authors.identifier: http://orcid.org/0000-0002-2506-0769
authors.initials: K
authors.lastname: Fujimori
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002957:Citrus / Q000737:chemistry*; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D005638:Fruit / Q000737:chemistry; D036701:Limonins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071161:Forkhead Box Protein O1; D036701:Limonins; D047495:PPAR gamma; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Citrus; FOXO1; adipocyte; limonoid