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

J Complement Integr Med. 2023 Jul 24;20(4):804-813. doi: 10.1515/jcim-2023-0137. eCollection 2023 Dec 1.

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.

Keywords: GLUT4; PPARγ; Penicillium citrinum; DEHP; adipogenesis; non-monotonic dose-response.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipogenesis*
  • Animals
  • Diethylhexyl Phthalate*
  • Glucose / metabolism
  • Glucose / pharmacology
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • PPAR gamma / pharmacology
  • Penicillium
  • Spectroscopy, Fourier Transform Infrared

Substances

  • PPAR gamma
  • phthalic acid
  • Diethylhexyl Phthalate
  • Glucose Transporter Type 4
  • Glucose

Supplementary concepts

  • Penicillium citrinum