Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells

PLoS One. 2018 Mar 29;13(3):e0193704. doi: 10.1371/journal.pone.0193704. eCollection 2018.


Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1 cells adipocyte differentiation and function in vitro. We found that CAde enhances terminal adipocyte differentiation of 3T3-L1 cells raising the expression of CCAAT/enhancer binding protein beta (C/Ebpβ), peroxisome proliferator activated receptor gamma (Pparγ), glucose transporter type 4 (Glut4) and fatty acid binding protein 4 (Fabp4). CAde improves insulin-induced glucose uptake of 3T3-L1 adipocytes, as well. A focused analysis of the phases occurring in the pre-adipocytes differentiation to mature adipocytes furthermore revealed that CAde promotes the early differentiation stage by up-regulating C/ebpβ expression at 2, 4 and 8 h post the adipogenic induction and anticipating the 3T3-L1 cell cycle entry and progression during mitotic clonal expansion (MCE). These findings provide evidence that the exposure to CAde enhances in vitro fat cell differentiation of pre-adipocytes and functional capacity of mature adipocytes, and pave the way to the development of products derived from Citrus aurantium L. fruit juice, which may improve WAT functional capacity and may be effective for the prevention and/or treatment of T2D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Animals
  • Biological Transport / drug effects
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Citrus / chemistry*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Glucose / metabolism
  • Mice
  • Plant Extracts / pharmacology*


  • CCAAT-Enhancer-Binding Protein-beta
  • Cyclic AMP Response Element-Binding Protein
  • Plant Extracts
  • Glucose

Associated data

  • figshare/5962027

Grant support

This study was funded by the European Foundation for the Study of Diabetes (EFSD) to CM, by the Ministero dell'Istruzione, Università e della Ricerca Scientifica (MIUR) (grants PRIN and FIRB-MERIT and PON01_02460 to FB) and by the Italian Diabete Ricerca Foundation and Eli Lilly S.p.a. to GAR.