Bitter Orange (Citrus aurantium Linné) Improves Obesity by Regulating Adipogenesis and Thermogenesis through AMPK Activation

Nutrients. 2019 Aug 22;11(9):1988. doi: 10.3390/nu11091988.


Obesity is a global health threat. Herein, we evaluated the underlying mechanism of anti-obese features of bitter orange (Citrus aurantium Linné, CA). Eight-week-administration of CA in high fat diet-induced obese C57BL/6 mice resulted in a significant decrease of body weight, adipose tissue weight and serum cholesterol. In further in vitro studies, we observed decreased lipid droplets in CA-treated 3T3-L1 adipocytes. Suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha indicated CA-inhibited adipogenesis. Moreover, CA-treated primary cultured brown adipocytes displayed increased differentiation associated with elevation of thermogenic factors including uncoupling protein 1 and PPARγ coactivator 1 alpha as well. The effects of CA in both adipocytes were abolished in AMP-activated protein kinase alpha (AMPKα)-suppressed environments, suggesting the anti-adipogenic and pro-thermogenic actions of CA were dependent on AMPKα pathway. In conclusion, our results suggest CA as a potential anti-obese agent which regulates adipogenesis and thermogenesis via AMPKα.

Keywords: AMP-activated protein kinase; adipogenesis; bitter orange; obesity; thermogenesis.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes, Brown / drug effects
  • Adipocytes, Brown / enzymology
  • Adipocytes, White / drug effects
  • Adipocytes, White / enzymology
  • Adipogenesis / drug effects*
  • Adipose Tissue / drug effects*
  • Adipose Tissue / enzymology
  • Adipose Tissue / physiopathology
  • Animals
  • Anti-Obesity Agents / isolation & purification
  • Anti-Obesity Agents / pharmacology*
  • Citrus* / chemistry
  • Diet, High-Fat*
  • Disease Models, Animal
  • Enzyme Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / enzymology
  • Obesity / physiopathology
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Signal Transduction
  • Thermogenesis / drug effects*


  • Anti-Obesity Agents
  • Plant Extracts
  • AMP-Activated Protein Kinases