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J Agric Food Chem. 2016 Dec 28;64(51):9607-9615. doi: 10.1021/acs.jafc.6b04521. Epub 2016 Dec 15.

A Limonoid Kihadanin B from Immature Citrus unshiu Peels Suppresses Adipogenesis through Repression of the Akt-FOXO1-PPARγ Axis in Adipocytes.

Author information

1
Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
2
Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences , 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

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.

KEYWORDS:

Akt; Citrus; FOXO1; adipocyte; limonoid

PMID:
27977180
DOI:
10.1021/acs.jafc.6b04521
[Indexed for MEDLINE]

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