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

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


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.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Citrus / chemistry*
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism*
  • Fruit / chemistry
  • Limonins / chemistry
  • Limonins / pharmacology*
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*


  • Forkhead Box Protein O1
  • Limonins
  • PPAR gamma
  • Plant Extracts
  • Proto-Oncogene Proteins c-akt