Bis‐(2‐ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster

Abstract

Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers, and human beings are exposed to DEHP via polyvinyl chloride (PVC) materials, medical equipment and even drinking water. While DEHP has been implicated to influence metabolism and endocrine functions, important questions remain about the molecular mechanisms of these effects. We employed the model organism Drosophila melanogaster and examined physiological, molecular and behavioural effects from DEHP-contaminated food. We found that DEHP, at levels comparable to human exposure, made male flies more resistant to starvation and increased lipid levels, while decreasing circulating carbohydrates. Moreover, DEHP-fed male flies had higher expression levels of an insulin-like peptide known to regulate metabolism, as well as the insulin receptor. Our results suggest that longterm DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions.Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers in manufacturing polyvinyl chloride (PVC) products [1]. Marked leaching into the environment occurs because phthalates are not covalently bound to the polymeric matrix. Human exposure to DEHP can occur via many routes, such as medical equipment, food containers and beverages, including drinking water. Although there are some limitations of using DEHP in food and devices, human exposure to excess DEHP is common. According to the United States Food and Drug Administration (FDA), medical devices made with PVC release DEHP into the body at levels up to 10 times higher than the tolerable daily intake (TDI) level [2]. In 2010, a review by the European Chemicals Agency (ECHA) announced that high levels of DEHP metabolites were detected in breastmilk, urine and other body fluid samples [3][4][5], while a survey conducted in Germany showed approximately 12% of the population exceeded the TDI value [6]. Thus, investigating how DEHP may disrupt metabolism is an important human health issue.Chronic exposure to DEHP and its oxidized metabolites may disrupt metabolism [7]. A study in rats found evidence that DEHP causes insulin resistance in adipose tissue via oxidation of glucose [8]. Studies also suggest that exposure to DEHP may affect mammalian reproductive ability [9-11] and development [12,13]. In human beings, DEHP metabolites, such as mono(2-ethyl-5-oxo-hexyl) phthalate (5oxo-MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (6-OH-MEHP), which increase in urine with age and weight [14], positively correlate with obesity and insulin resistance [15,16].Importantly, in children aged less than 3 months, the glucuronidation pathway is still immature, which may cause increased internal concentrations of these toxic metabolites [17,18].However, it is unclear how DEHP interferes with metabolic pathways. To investigate the disruptive effects of DEHP, we employed Drosophila melanogast...

Analysis of the impact of three phthalates on the freshwater gastropod Physella acuta at the transcriptional level

“…diversicolor , DBP affects oxidative stress, lipid and energy metabolism, and osmoregulation 17 . In other invertebrates, including Chironomus riparius 42 , Drosophila melanogaster 43 , and Caenorhabditis elegans 15 , phthalates alter endocrine pathways. The changes affect the ecdysone response as well as the expression of insulin-like peptide.…”

Maternal Urinary Phthalate Metabolites are Associated with Lipidomic Signatures Among Pregnant Women in Puerto Rico

“…The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07. 19.21260700 doi: medRxiv preprint Our previous research in the Puerto Rico PROTECT birth cohort found associations between prenatal phthalate urine metabolite levels and increased odds of preterm birth [28,29]. In the PROTECT cohort, we also assessed the relationship between maternal lipidomic profiles and adverse birth outcomes and observed numerous significant lipid signatures for spontaneous preterm birth [30].…”

“…One of the proposed mechanisms of action and pathways involved in early life phthalateinduced adverse effects is disruption of lipids. Animal studies suggest that phthalates influence circulating lipid levels and lipid signaling [17][18][19][20], by interfering with peroxisome-proliferator active receptor gamma (PPARγ) [21,22]. This points to the possibility that a similar mechanism is at play for humans.…”

Consequences of Exposure to Phthalates, Micro Plastics and Nano-Plastics on the Organisms

“…DEHP dealing with possibly upsets sugar homeostasis and starts a diabeteslike metabolic brokenness (Coa et al, 2016). DBP effects insulin and make disturbance in male flies, by managing quality includes in lipid, glucose and xenobiotic digestion (Williams et al, 2016). DBP influence formative time and cause diminishes in the quantity of posterity in D. melanogaster (Atli, Emel, 2010).…”