Polychlorinated biphenyl 138 exposure-mediated lipid droplet enlargement endows adipocytes with resistance to TNF-α-induced cell death

Kim, Yeon A; Kim, Hye Young; Oh, Yoo Jin; Kwon, Woo Young; Lee, Sung Won; Bae, Ju Yong; Woo, Min Seok; Kim, Jong Min; Yoo, Young Hyun

doi:10.1016/j.toxlet.2018.04.029

Cited by 12 publications

(7 citation statements)

References 21 publications

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“…Moreover, limited data detailing the effects of direct PCB exposure on body composition demonstrate conflicting results and utilize diet as a means to understand the influence of PCB exposure on fat and lean mass ( 20 , 39 ). Nonetheless, PCBs have been demonstrated to alter adipocyte development ( 21 , 24 , 25 , 41 ) and death ( 25 ), and as a result have been deemed as obesogens. Further, direct PCB exposure has been shown to induce impairments in glucose ( 17 , 18 , 21 , 23 , 39 , 40 , 42 ) and insulin ( 21 , 22 , 39 ) tolerance.…”

Section: Discussionmentioning

confidence: 99%

Lack of Offspring Nrf2 Does Not Exacerbate the Detrimental Metabolic Outcomes Caused by In Utero PCB126 Exposure

et al. 2021

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Human environmental exposures to toxicants, such as polychlorinated biphenyls (PCBs), increase oxidative stress and disease susceptibility. Such exposures during pregnancy and/or nursing have been demonstrated to adversely affect offspring health outcomes. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the antioxidant response and is involved in the detoxification of coplanar PCBs, like PCB126. The purpose of this study was to investigate glucose tolerance and body composition in PCB-exposed offspring expressing or lacking Nrf2. We hypothesized that offspring lacking Nrf2 expression would be more susceptible to the long-term health detriments associated with perinatal PCB exposure. During gestation, whole-body Nrf2 heterozygous (Het) and whole-body Nrf2 knockout (KO) mice were exposed to vehicle or PCB126. Shortly after birth, litters were cross-fostered to unexposed dams to prevent PCB exposure during nursing. Offspring were weaned, and their body weight, body composition, and glucose tolerance were recorded. At two months of age, PCB exposure resulted in a significant reduction in the average body weight of offspring born to Nrf2 Het dams (p < 0.001) that primarily arose from the decrease in average lean body mass in offspring (p < 0.001). There were no differences in average body weight of PCB-exposed offspring born to Nrf2 KO dams (p > 0.05), and this was because offspring of Nrf2 KO dams exposed to PCB126 during pregnancy experienced a significant elevation in fat mass (p = 0.002) that offset the significant reduction in average lean mass (p < 0.001). Regardless, the lack of Nrf2 expression in the offspring themselves did not enhance the differences observed. After an oral glucose challenge, PCB-exposed offspring exhibited significant impairments in glucose disposal and uptake (p < 0.05). Offspring born to Nrf2 Het dams exhibited these impairments at 30 min and 120 min, while offspring born to Nrf2 KO dams exhibited these impairments at zero, 15, 30, 60 and 120 min after the glucose challenge. Again, the interactions between offspring genotype and PCB exposure were not significant. These findings were largely consistent as the offspring reached four months of age and demonstrate that the lack of offspring Nrf2 expression does not worsen the metabolic derangements caused by in utero PCB exposure as we expected. Future directions will focus on understanding how the observed maternal Nrf2 genotypic differences can influence offspring metabolic responses to in utero PCB exposure.

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Section: Discussionmentioning

confidence: 99%

Lack of Offspring Nrf2 Does Not Exacerbate the Detrimental Metabolic Outcomes Caused by In Utero PCB126 Exposure

et al. 2021

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“…In that study, we elucidated that LD enlargement induced by PCB-138 confers adipocytes the resistance to TNF-α-induced cell death. In addition, we elicited that Fsp27, perilipin, and survivin, at least in part, are involved in sustaining enlarged LDs, which contributes to the induction of obesity and subsequent insulin resistance [110].…”

Section: Experimental Animal Studies Investigating the Mechanism Umentioning

confidence: 99%

Persistent Organic Pollutant-Mediated Insulin Resistance

Kim

Woo

Lee

et al. 2019

IJERPH

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Persistent organic pollutants (POPs) such as organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have become wide-spread environmental contaminants as a consequence of their extensive use, long-range transport, and persistence. Because POPs are highly resistant to metabolic degradation, humans bioaccumulate these lipophilic and hydrophobic pollutants in fatty tissues for many years. Previous studies have demonstrated that POPs including PCBs are involved in the development of diabetes mellitus (DM) type 2 and insulin resistance. Numerous epidemiological studies suggest an association between POP burden and DM type 2/metabolic syndrome. In addition, several experimental studies have provided additional evidence supporting the association between POP exposure and DM type 2 or insulin resistance. Epidemiological and experimental studies have provided compelling evidence indicating that exposure to POPs increases the risk of developing insulin resistance and metabolic disorders. However, the detailed molecular mechanism underlying POP-induced insulin resistance is yet to be elucidated. In this article, we review literature that has reported on the association between POP burden and insulin resistance and the mechanism underlying POP-induced insulin resistance, and discuss implications for public health.

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“…Independent of perinatal exposures, PCBs have been demonstrated to increase body weight ( 20 , 22 , 40 – 42 ). Studies demonstrating the impact of PCB exposure to body composition indicate that PCB-induced obesity may occur via alteration of adipocyte development ( 20 , 21 , 43 , 44 ) and death ( 44 ). However, the route, dose, and timing of coplanar/non-coplanar PCBs or mixtures exposures must be considered to avoid overinterpretation of the comparisons to previous studies.…”

Section: Discussionmentioning

confidence: 99%

Exposure to PCB126 during the nursing period reversibly impacts early-life glucose tolerance

et al. 2023

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Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal days (PND) 3, 10, and 17 (n = 9 per group). Offspring body weight, lean and fat mass, and glucose tolerance were recorded every three weeks. PCB126 treatment did not alter dam nor offspring body weight (p > 0.05). PCB126-exposed male and female offspring displayed normal body composition (p > 0.05) relative to vehicle-exposed offspring. However, both male and female offspring that were exposed to PCB126 during the nursing period had significantly impaired glucose tolerance at 3 and 9 weeks of age (p < 0.05). At 6 and 12 weeks of age, no impairments in glucose tolerance existed in offspring (p > 0.05). Our current study demonstrates that exposure to PCB126 through the mother’s milk does not affect short- or long-term body composition but impairs glucose tolerance in the short-term.

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Polychlorinated biphenyl 138 exposure-mediated lipid droplet enlargement endows adipocytes with resistance to TNF-α-induced cell death

Cited by 12 publications

References 21 publications

Lack of Offspring Nrf2 Does Not Exacerbate the Detrimental Metabolic Outcomes Caused by In Utero PCB126 Exposure

Lack of Offspring Nrf2 Does Not Exacerbate the Detrimental Metabolic Outcomes Caused by In Utero PCB126 Exposure

Persistent Organic Pollutant-Mediated Insulin Resistance

Exposure to PCB126 during the nursing period reversibly impacts early-life glucose tolerance

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