Chronic DDE Exposure Modifies Mitochondrial Respiration during Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Mature Adipocytes.

Iva Kladnicka,Jan Jedlicka,Monika Bludovska,Jitka Kuncova,Michaela Kohoutova,Ludek Muller,Miroslava Cedikova,Dana Mullerova,Iveta Plavinova,Michaela Kripnerova

doi:10.3390/biom11081068

Iva Kladnicka, Jan Jedlicka + Show 8 more

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https://doi.org/10.3390/biom11081068

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Journal: Biomolecules	Publication Date: Jul 21, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Charles University, University of West Bohemia

Abstract

The contribution of environmental pollutants to the obesity pandemic is still not yet fully recognized. Elucidating possible cellular and molecular mechanisms of their effects is of high importance. Our study aimed to evaluate the effect of chronic, 21-day-long, 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p´-DDE) exposure of human adipose-derived mesenchymal stem cells committed to adipogenesis on mitochondrial oxygen consumption on days 4, 10, and 21. In addition, the mitochondrial membrane potential (MMP), the quality of the mitochondrial network, and lipid accumulation in maturing cells were evaluated. Compared to control differentiating adipocytes, exposure to p,p´-DDE at 1 μM concentration significantly increased basal (routine) mitochondrial respiration, ATP-linked oxygen consumption and MMP of intact cells on day 21 of adipogenesis. In contrast, higher pollutant concentration seemed to slow down the gradual increase in ATP-linked oxygen consumption typical for normal adipogenesis. Organochlorine p,p´-DDE did not alter citrate synthase activity. In conclusion, in vitro 1 μM p,p´-DDE corresponding to human exposure is able to increase the mitochondrial respiration per individual mitochondrion at the end of adipocyte maturation. Our data reveal that long-lasting exposure to p,p´-DDE could interfere with the metabolic programming of mature adipocytes.

Highlights

In adipocytes differentiating in the presence of 1 μM DDE, routine oxygen consumption further increased on day 21 of the experiment and became significantly different compared to both dimethyl sulfoxide (DMSO) and differentiation medium (DM) controls (Figure 5A)
10 μM adipocytes, the leak respiration was very similar on days 4 and 10 (11.6 ± 2.9 and the presence of 1 μM DDE, routine oxygen consumption further increased on day 21 of the experiment and became significantly different compared to both DMSO and DM controls (Figure 5A)
This study focused on the impact of DDE on the metabolic characteristic of human adipose-derived mesenchymal stem cells (hADMSCs) in the whole course of differentiation (21 days)

Summary

Introduction

Adipose tissue is a complex heterogeneous and highly dynamic organ performing many functions. It contributes to the control of energy metabolism of the whole organism. The specific function of adipose tissue is to provide mature adipocytes, i.e., cells that are able to store energy in lipid droplets in the form of triglycerides and release it in the chemical or thermal form according to the body requirements [1]. Adipogenesis, the process during which the mature adipocytes differentiate from their precursors, mesenchymal stem cells, is necessary for the dynamic renewal and optimal function of adipose tissue.

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