In Vitro effect of DDE exposure on the regulation of lipid metabolism and secretion in McA-RH7777 hepatocytes: A potential role in dyslipidemia which may increase the risk of type 2 diabetes mellitus

Ward, Antonio; Dail, Mary Beth; Chambers, Janice E.

doi:10.1016/j.tiv.2016.08.011

Cited by 15 publications

(13 citation statements)

References 41 publications

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“…The mechanism of action of p,p'-DDT and p,p'-DDE on BMI increase remains uncertain. In vitro studies suggested that these chemicals may be endocrine disruptors [43], and that they could impair lipid secretion and metabolism [44]. In rat models, perinatal exposure to a commercial formulation of DDT can induce thermogenesis and lipid metabolism disruptions, especially in female offspring [14], and could induce transgenerational obesity [15].…”

Section: Discussionmentioning

confidence: 99%

Estimated postnatal p,p’-DDT and p,p’-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children

et al. 2020

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Background: Children are exposed to p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'dichlorodiphenyldichloroethylene (p,p'-DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children's exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age. Methods: We used data from a birth cohort (n = 290) of the Tohoku Study of Child Development. p,p'-DDT and p, p'-DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0-6 months, 6-12 months, 12-24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models. Results: We found no significant association between levels of p,p'-DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimated p,p'-DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimated p,p'-DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0-6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6-12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12-24 months exposure period. Conclusion: In this study of Japanese children, estimated postnatal p,p'-DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that earlylife exposure to p,p'-DDE may be associated with higher BMI during childhood.

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Section: Discussionmentioning

confidence: 99%

Estimated postnatal p,p’-DDT and p,p’-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children

et al. 2020

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“…Our current data indicate direct exposure to trans‐nonachlor has a greater steatotic effect than exposure to DDE or oxychlordane with significant increases in intracellular neutral lipid accumulation following 24 and 48 hours of trans‐nonachlor exposure compared to nonsignificant increases following exposure to oxychlordane and DDE. Ward et al (2016) recently demonstrated exposure to DDE (10 μM) significantly decreased OA‐induced intracellular neutral lipid accumulation in McA hepatoma cells . Additionally, Liu et al (2017) demonstrated exposure to DDE increases neutral lipid accumulation with significant increases in fatty acid composition in human HepG2 hepatoma cells .…”

Section: Discussionmentioning

confidence: 99%

“…Ward et al (2016) recently demonstrated exposure to DDE (10 μM) significantly decreased OA-induced intracellular neutral lipid accumulation in McA hepatoma cells. 15 Additionally, Liu et al (2017) demonstrated exposure to DDE increases neutral lipid accumulation with significant increases in fatty acid composition in human HepG2 hepatoma cells. 16 Thus, there are discrepancies in the currently observed effects of DDE on intracellular lipid accumulation in the current study and those previously reported in the literature which may be due to a difference in the cell type which was utilized in each study.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to POPs typically consists of exposure to a mixture of compounds, the relative contribution of individual POPs which comprise these mixtures to the promotion of alterations in hepatic lipid metabolism is not well known. Recent studies by Ward et al demonstrated exposure to DDE, a highly prevalent POP, exacerbates fatty acid‐induced apolipoprotein B (APOB) secretion while decreasing neutral lipid accumulation in a hepatoma model of liver function . In addition, Liu et al (2017) demonstrated increased lipid accumulation following exposure to DDE and β‐hexachlorohexane (β‐HCH) in human HepG2 cells .…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies by Ward et al (2016) demonstrated exposure to DDE, a highly prevalent POP, exacerbates fatty acid-induced apolipoprotein B (APOB) secretion while decreasing neutral lipid accumulation in a hepatoma model of liver function. 15 In addition, Liu et al (2017) demonstrated increased lipid accumulation following exposure to DDE and β-hexachlorohexane (β-HCH) in human HepG2 cells. 16 Thus, these recent studies indicate POPs exposure can have a direct effect on the hepatocyte to alter hepatic lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans‐nonachlor in rat primary hepatocytes

Howell

McDevitt

Henein

et al. 2018

Environmental Toxicology

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Recent epidemiological studies have revealed significant positive associations between exposure to organochlorine (OC) pesticides and occurrence of the metabolic syndrome and there are a growing number of animal-based studies to support causality. However, the cellular mechanisms linking OC compound exposure and metabolic dysfunction remain elusive. Therefore, the present study was designed to determine if direct exposure to three highly implicated OC compounds promoted hepatic steatosis, the hepatic ramification of the metabolic syndrome. First, the steatotic effect of p,p'-dichlorodiphenyldichloroethylene (DDE), oxychlordane, and trans-nonachlor was determined in freshly isolated rat primary hepatocytes. Exposure to trans-nonachlor significantly increased neutral lipid accumulation as opposed to DDE and oxychlordane. To determine possible mechanisms governing increased fatty acid availability, the effects of trans-nonachlor exposure on fatty acid uptake, de novo lipogenesis, triglyceride secretion, and fatty acid oxidation were explored. Trans-nonachlor did not significantly alter fatty acid uptake. However, insulin-stimulated de novo lipogenesis as well as basal expression of fatty acid synthase, a major regulator of lipogenesis were significantly increased following trans-nonachlor exposure. Interestingly, there was a significant decrease in fatty acid oxidation following trans-nonachlor exposure. This decrease in fatty acid oxidation was accompanied by a slight, but significant increase in oleic acid-induced cellular triglyceride secretion. Therefore, taken together, the present data indicate direct exposure to trans-nonachlor has a more potent pro-steatotic effect than exposure to DDE or oxychlordane. This pro-steatotic effect of trans-nonachlor appears to be predominately mediated via increased de novo lipogenesis and decreased fatty acid oxidation.

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Transcriptome analysis reveals global gene expression changes of Chilo suppressalis in response to sublethal dose of chlorantraniliprole

et al. 2019

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In Vitro effect of DDE exposure on the regulation of lipid metabolism and secretion in McA-RH7777 hepatocytes: A potential role in dyslipidemia which may increase the risk of type 2 diabetes mellitus

Cited by 15 publications

References 41 publications

Estimated postnatal p,p’-DDT and p,p’-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children

Estimated postnatal p,p’-DDT and p,p’-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children

Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans‐nonachlor in rat primary hepatocytes

Transcriptome analysis reveals global gene expression changes of Chilo suppressalis in response to sublethal dose of chlorantraniliprole

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