Archives of Pharmacal Research

, Volume 40, Issue 11, pp 1336–1343 | Cite as

Novel anti-adipogenic activity of anti-malarial amodiaquine through suppression of PPARγ activity

Research Article

Abstract

Amodiaquine (AQ) was developed as a selective drug against Plasmodium falciparum malaria infection and has received increasing attention as a therapeutic agent for the treatment of rheumatoid arthritis, Parkinson’s disease, and cancer due to its anti-inflammatory, anti-proliferative, and autophagic–lysosomal blockade properties. As autophagy activation is involved in promoting adipogenic differentiation, we examined whether anti-autophagic AQ affected adipocyte differentiation of 3T3-L1 pre-adipocytes. AQ dose-dependently and significantly suppressed adipocyte differentiation in conjunction with decreases in lipid droplet formation and expression of adipogenic markers including adiponectin, adipocyte fatty acid-binding protein 2 (aP2), resistin, and leptin. Although peroxisome proliferator-activated receptor γ (PPARγ) decreases by inhibition of autophagy, AQ treatment did not induce PPARγ degradation despite the suppression of autophagolysosomal degradation. Instead, AQ suppressed the PPARγ activity to transcriptionally activate the aP2 gene transcription through the selective prevention of nuclear localization of PPARγ. These results demonstrated the novel anti-adipogenic activity of AQ and identified its underlying mechanism that AQ suppressed adipogenic gene expression and lipid formation by inhibiting nuclear localization of PPARγ in an autophagy-independent manner. AQ is recommended as a safe and effective anti-obesity drug for controlling overweight and obesity.

Keywords

Amodiaquine Adipocyte differentiation Lipid accumulation PPARγ Nuclear localization 

Notes

Acknowledgements

We thank Dr. Kwang Soo Kim (Mclean Hospital, Boston, MA) for providing amodiaquine. This work was supported by Basic research program of the National Research Foundation (NRF-2016R1D1A1B03935951) funded by the Korean Government.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.

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Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  • Tae Hee Kim
    • 1
  • Hyo Kyeong Kim
    • 1
  • Eun Sook Hwang
    • 1
  1. 1.College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulKorea

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