High Fat Diet Feeding Exaggerates Perfluorooctanoic Acid-Induced Liver Injury in Mice via Modulating Multiple Metabolic Pathways

Tan, Xiaobing; Xie, Guoxiang; Sun, Xiuhua; Li, Qiong; Zhong, Wei; Qiao, Peter; Sun, Xinguo; Wang, Jia; Zhou, Zhanxiang

doi:10.1371/journal.pone.0061409

Cited by 75 publications

(75 citation statements)

References 41 publications

(43 reference statements)

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“…Likewise, associations between organochlorine pesticides or their metabolites and liver enzymes have been seen for ALT [562] and gamma glutamyl transferase [565]. Perfluorinated chemical exposures were also positively associated with ALT in NHANES [566], and this association was more evident for PFOA exposures in obese adults [567]. Positive associations were also seen between both PFOA and PFOS exposures in adult participants of the C8 study (n=47,092 subjects) [568].…”

Section: Mdcs and Metabolism-relevant Diseasesmentioning

confidence: 99%

Metabolism disrupting chemicals and metabolic disorders

Heindel

Blumberg

Cave

et al. 2017

Reproductive Toxicology

820

651

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The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations.

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Section: Mdcs and Metabolism-relevant Diseasesmentioning

confidence: 99%

Metabolism disrupting chemicals and metabolic disorders

Heindel

Blumberg

Cave

et al. 2017

Reproductive Toxicology

820

651

View full text Add to dashboard Cite

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“…In addition to BPA, other EDCs can enhance NAFLD when promoted by a HFD (for example, treatment of mice with PFOA 108 or the pesticides CYP or ATZ 109 ). Importantly, some EDC exposures alone failed to trigger disease, with NAFLD observed only when EDC exposure was combined with a HFD.…”

Section: Liver Fat Metabolism and Edcsmentioning

confidence: 99%

Endocrine-disrupting chemicals and fatty liver disease

et al. 2017

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Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic paralleling the increase in obesity and diabetes mellitus seen in Western diet-consuming countries. As NAFLD can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma (HCC), an understanding of factors that trigger its development and pathological progression is needed. Although by definition this disease is not associated with alcohol consumption, exposure to environmental agents that have been linked to other diseases might have a role in the development of NAFLD. Here, we focus on one class of these agents, endocrine-disrupting chemicals (EDCs), and their potential to influence the initiation and progression of a cascade of pathological conditions associated with fatty liver. Experimental studies have revealed several potential mechanisms by which EDC exposures might contribute to disease pathogenesis, including modulation of nuclear hormone receptor (NR) function and alteration of the epigenome. However, many questions remain to be addressed about the causal link between acute and chronic EDC exposure and the development of NAFLD in humans. Future studies that address these questions hold promise not only for understanding the linkage between EDC exposure and liver disease, but for elucidating the molecular mechanisms underpinning NAFLD and the development of new prevention and treatment opportunities.

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“…Several of these chemicals have previously been associated with fatty liver disease and TASH. These include metabolites of the solvents PCE and TCE [29]; the plasticizers DEHP [234] and bisphenol A (BPA) [235]; and the persistent organic pollutants PCBs [233], perfluorooctanoic acid [236], and some organochlorine insecticides [237]. Polymorphisms in nuclear receptors including PXR [70] and PPAR [238] have previously been associated with fatty liver disease.…”

Section: Nuclear Receptors In Ash Cash and Tashmentioning

confidence: 99%

Nuclear receptors and nonalcoholic fatty liver disease

Cave

Clair

Hardesty

et al. 2016

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

233

204

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Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic side effects. The impact of nuclear receptor crosstalk in NAFLD is likely to be profound, but requires further elucidation. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

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High Fat Diet Feeding Exaggerates Perfluorooctanoic Acid-Induced Liver Injury in Mice via Modulating Multiple Metabolic Pathways

Cited by 75 publications

References 41 publications

Metabolism disrupting chemicals and metabolic disorders

Metabolism disrupting chemicals and metabolic disorders

Endocrine-disrupting chemicals and fatty liver disease

Nuclear receptors and nonalcoholic fatty liver disease

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