Non-monotonic dose-response of di-(2-ethylhexyl) phthalate isolated from Penicillium citrinum XT6 on adipogenesis and expression of PPARγ and GLUT4 in 3T3-L1 adipocytes

Author:

Fauziah Fitra12ORCID,Ali Hirowati34ORCID,Ilmiawati Cimi5ORCID,Ariyanto Eko Fuji67ORCID,Bakhtra Dwi Dinni Aulia2ORCID,Mita Deslina Setria2,Syafni Nova8ORCID,Handayani Dian8ORCID

Affiliation:

1. Doctoral Program, Graduate School of Biomedical Science, Faculty of Medicine , Universitas Andalas , Padang , Indonesia

2. School of Pharmaceutical Science Padang (STIFARM Padang) , Padang , Indonesia

3. Department of Biochemistry, Undergraduate Program of Medicine, Faculty of Medicine , Universitas Andalas , Padang , Indonesia

4. Biomedical Laboratory, Center for Integrative Biomedical Research, Faculty of Medicine , Universitas Andalas , Padang , Indonesia

5. Department of Pharmacology, Undergraduate Program of Medicine, Faculty of Medicine , Universitas Andalas , Padang , Indonesia

6. Division of Biochemistry and Molecular Biology, Department of Biomedical Sciences, Faculty of Medicine , Universitas Padjadjaran , Sumedang , Indonesia

7. Research Center for Medical Genetics, Faculty of Medicine , Universitas Padjadjaran , Bandung , Indonesia

8. Laboratory of Sumatran Biota/Faculty of Pharmacy , Universitas Andalas , Padang , Indonesia

Abstract

Abstract Objectives Adipogenesis is the fat cell formation process regulated by peroxisome proliferator-activated receptors (PPARγ). The insulin-responsive glucose transporter 4 (GLUT4) has a major role in glucose uptake and metabolism in insulin target tissues (i.e., adipose and muscle cells). The interplay between PPARγ and GLUT4 is essential for proper glucose homeostasis. This study aimed to isolate, elucidate, and investigate the effect of an isolated compound from Penicillium citrinum XT6 on adipogenesis, PPARγ, and GLUT4 expression in 3T3-L1 adipocytes. Methods The isolated compound was determined by analyzing spectroscopic data (LC-MS, FT-IR, Spectrophotometry UV–Vis, and NMR). The adipogenesis activity of the isolated compound in 3T3-L1 cells was determined by the Oil Red O staining method. RT-PCR was used to analyze the gene expression of PPARγ and GLUT4. Results Di-(2-ethylhexyl)-phthalate (DEHP) was the isolated compound from P.citrinum XT6. The results revealed adipogenesis stimulation and inhibition, as well as PPARγ and GLUT4 expressions. Conclusions DEHP showed a non-monotonic dose-response (NMDR) effect on adipogenesis and PPARγ and GLUT4 expression. It is the first study that reveals DEHP’s NMDR effects on lipid and glucose metabolism in adipocytes.

Funder

Doctoral Dissertation Grant Program from The Ministry of Research and Technology

Publisher

Walter de Gruyter GmbH

Subject

Complementary and alternative medicine

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