Effects of dietary polychlorinated biphenyls on cholesterol catabolism in rats

Nagaoka, Satoshi; Miyazaki, Hitoshi; Aoyama, Yumi; Yoshida, Akira

doi:10.1079/bjn19900018

Cited by 12 publications

(7 citation statements)

References 30 publications

(33 reference statements)

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“…There is compelling evidence that decreasing total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL) can help markedly reduce a patient's risk of CVD (European Association for Cardiovascular et al 2011, Tenenbaum et al 2014). Similar to findings on the association between obesity and PCB exposure, the most compelling and complete evidence comes from laboratory studies (Bell et al 1994, Hitomi &Yoshida 1989, Nagaoka et al 1986, Nagaoka et al 1990, Oda et al 1990). For instance, ApoE (-/-) mice injected with PCB 77 exhibited increased serum cholesterol and atherosclerosis (Arsenescu et al 2008).…”

Section: Epidemiological Studies Linking Pcbs and Cardiovascular Disementioning

confidence: 78%

Polychlorinated biphenyls and links to cardiovascular disease

Perkins

Petriello

Newsome

et al. 2015

Environ Sci Pollut Res

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The pathology of cardiovascular disease is multi-faceted, with links to many modifiable and non-modifiable risk factors. Epidemiological evidence now implicates exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), with an increased risk of developing diabetes, hypertension, and obesity; all of which are clinically relevant to the onset and progression of cardiovascular disease. PCBs exert their cardiovascular toxicity either directly or indirectly via multiple mechanisms, which are highly dependent on the type and concentration of PCBs present. However, many PCBs may modulate cellular signaling pathways leading to common detrimental outcomes including induction of chronic oxidative stress, inflammation, and endocrine disruption. With the abundance of potential toxic pollutants increasing globally, it is critical to identify sensible means of decreasing associated disease risks. Emerging evidence now implicates a protective role of lifestyle modifications such as increased exercise and/or nutritional modulation via anti-inflammatory foods, which may help to decrease the vascular toxicity of PCBs. This review will outline the current state of knowledge linking coplanar and non-coplanar PCBs to cardiovascular disease and describe the possible molecular mechanism of this association.

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Section: Epidemiological Studies Linking Pcbs and Cardiovascular Disementioning

confidence: 78%

Polychlorinated biphenyls and links to cardiovascular disease

Perkins

Petriello

Newsome

et al. 2015

Environ Sci Pollut Res

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“…Previous investigators demonstrated that dietary exposure to PCBs results in fatty liver and hypercholesterolemia in rats (Kato et al 1980; Nagaoka et al 1990; Quazi et al 1983). These effects were primarily attributed to an increase in hepatic cholesterol synthesis.…”

Section: Discussionmentioning

confidence: 99%

Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis

Arsenescu¹,

Arsenescu²,

King

et al. 2008

Environ Health Perspect

281

258

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BackgroundObesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown.ObjectivesIn this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis.MethodsPCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis.ResultsLow concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis.ConclusionsOur findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.

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“…For instance, higher bisphenol A (BPA) exposure has been consistently associated with CVD in multiple large-scale human population studies (4,5,7). Exposure to certain polychlorinated biphenyls (PCBs) induces hypercholesterolemia and promotes atherosclerosis in animals (8,9). Circulating PCB levels have been associated with atherosclerotic plaques in the elderly (10).…”

mentioning

confidence: 99%

Intestinal Pregnane X Receptor Links Xenobiotic Exposure and Hypercholesterolemia

Sui

Helsley

Park

et al. 2015

Molecular Endocrinology

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Recent studies have associated endocrine-disrupting chemical (EDC) exposure with the increased risk of cardiovascular disease in humans, but the underlying mechanisms responsible for these associations remain elusive. Many EDCs have been implicated in activation of the nuclear receptor pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism in the liver and intestine. Here we report an important role of intestinal PXR in linking xenobiotic exposure and hyperlipidemia. We identified tributyl citrate (TBC), one of a large group of Food and Drug Administration-approved plasticizers for pharmaceutical or food applications, as a potent and selective PXR agonist. TBC efficiently activated PXR and induced PXR target gene expression in vitro and in vivo. Interestingly, TBC activated intestinal PXR but did not affect hepatic PXR activity. Exposure to TBC increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice. TBC-mediated PXR activation stimulated the expression of an essential cholesterol transporter, Niemann-Pick C1-like 1 (NPC1L1), in the intestine. Promoter analysis revealed a DR-4 type of PXR response element in the human NPC1L1 promoter, and TBC promoted PXR recruitment onto the NPC1L1 promoter. Consistently, TBC treatment significantly increased lipid uptake by human and murine intestinal cells and deficiency of PXR inhibited TBC-elicited lipid uptake. These findings provide critical mechanistic insight for understanding the impact of EDC-mediated PXR activation on lipid homeostasis and demonstrate a potential role of PXR in mediating the adverse effects of EDCs on cardiovascular disease risk in humans.

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Effects of dietary polychlorinated biphenyls on cholesterol catabolism in rats

Cited by 12 publications

References 30 publications

Polychlorinated biphenyls and links to cardiovascular disease

Polychlorinated biphenyls and links to cardiovascular disease

Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis

Intestinal Pregnane X Receptor Links Xenobiotic Exposure and Hypercholesterolemia

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