A New Selective PPARγ Modulator Inhibits Triglycerides Accumulation during Murine Adipocytes’ and Human Adipose-Derived Mesenchymal Stem Cells Differentiation

International Journal of Molecular Sciences

Stephana Carelli¹  GianVicenzo Zuccotti¹  Federica Rey²  Alfredo Gorio²  Toniella Giallongo²  Ghina Al Haj²  Mattia Colli²  AnnaMaria Di Giulio³  Barbara Marzani⁴  Giammaria Giuliani⁴ 

[1] Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy;Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy;Pediatric Research Center “Romeo ed Enrica Invernizzi”, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy;Research and Development, Giuliani SpA, Via Pelagio Palagi, 2, 20129 Milan, Italy;

关键词: adipocytes;    differentiation;    lipogenesis;    PPAR γ modulator;    adipogenesis;   

DOI  :  10.3390/ijms21124415

来源: DOAJ

【 摘 要 】

Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome proliferator-activated receptor γ (PPARγ) modulator, during adipose differentiation of murine pre-adipocytes and human Adipose Derived Stem Cells (hADSCs). We differentiated 3T3-L1 cells and primary hADSCs in the presence of various doses of GMG-43AC and evaluated the differentiation efficiency measuring lipid accumulation, the expression of specific differentiation markers and the quantification of accumulated triglycerides. The treatment with GMG-43AC is not toxic as shown by cell viability assessments after the treatments. Our findings demonstrate the inhibition of lipid accumulation and the significant decrease in the expression of adipocyte-specific genes, such as PPARγ, FABP-4, and leptin. This effect was long lasting, as the removal of GMG-43AC from culture medium did not allow the restoration of adipogenic process. The above actions were confirmed in hADSCs exposed to adipogenic stimuli. Together, these results indicate that GMG-43AC efficiently inhibits adipocytes differentiation in murine and human cells, suggesting its possible function in the reversal of adipogenesis and modulation of lipolysis.

【 授权许可】

Unknown