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

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.

Exposure to 4,4′‐DDE in visceral adipose tissue and weight loss in adolescents from the Teen‐LABS cohort

“…Adipose tissue plays an active role in the body's regulation of appetite and inflammatory responses. DDE can upregulate adipogenesis by stimulating adipogenic pathways that promote adipocyte hyperplasia [19,39]. Significant weight loss leads to an increase in plasma levels of adiponectin, a signaling peptide that regulates the metabolism of lipids and glucose, and a decrease in levels of leptin, a hormone involved in regulation of energy balance and appetite [40,41].…”

Obesogens in Foods

“…Breast-feeding is another important form of human exposure. A growing amount of epidemiological evidence, in both in vivo and in vitro studies, have associated persistent organic pollutants, such as DDT and the DDT metabolite p,p'-DDE, with obesity [90][91][92][93]. Acute exposure causes harm to the central nervous system, while chronic exposure can result in liver cancer, disruption of endocrine control, harm of the fetus and fertility, and increased risk of Type 2 diabetes.…”

Recent Advances in Translational Adipose-Derived Stem Cell Biology

“…If addition to their paracrine activity, ASCs mediate regeneration via direct differentiation if the organ or tissue affected by degeneration is mesodermal (e.g., bone, fat tissue or cartilage). In this context, Kladnicka et al [10] demonstrated that chronic exposure of ASCs to the environmental pollutant 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p'-DDE) modifies mitochondrial respiration during adipogenic differentiation. Since this phenomenon could bias ASCs towards adipogenesis, these results provide a potential link between environmental pollutants produced during the Anthropocene epoch and the current obesity epidemic especially prevalent in developed and developing countries.…”