Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants

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Abstract

Background: Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions.

Objectives: In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms.

Methods: We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT.

Discussion: As a storage compartment for lipophilic POPs, AT plays a critical role in the toxicokinetics of a variety of drugs and pollutants, in particular, POPs. By sequestering POPs, AT can protect other organs and tissues from POPs overload. However, this protective function could prove to be a threat in the long run. The accumulation of lipophilic POPs will increase total body burden. These accumulated POPs are slowly released into the bloodstream, and more so during weight loss. Thus, AT constitutes a continual source of internal exposure to POPs. In addition to its buffering function, AT is also a target of POPs and may mediate part of their metabolic effects. This is particularly relevant because many POPs induce obesogenic effects that may lead to quantitative and qualitative alterations of AT. Some POPs also induce a proinflammatory state in AT, which may lead to detrimental metabolic effects.

Conclusion: AT appears to play diverse functions both as a modulator and as a target of POPs toxicity.

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Rapid DNA methylation changes after exposure to traffic particles.

Andrea A. Baccarelli, Robert O Wright, Valentina Bollati … (2009)

Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis. We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome. We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction-pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter 0.12). We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined.

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Fibrosis in Human Adipose Tissue: Composition, Distribution, and Link With Lipid Metabolism and Fat Mass Loss

Adeline Divoux, Joan Tordjman, Danièle Lacasa … (2010)

OBJECTIVE Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and omental WAT (oWAT) fibrosis in obesity and its relationship with metabolic alterations and surgery-induced weight loss. RESEARCH DESIGN AND METHODS Surgical biopsies for scWAT and oWAT were obtained in 65 obese (BMI 48.2 ± 0.8 kg/m2) and 9 lean subjects (BMI 22.8 ± 0.7 kg/m2). Obese subjects who were candidates for bariatric surgery were clinically characterized before, 3, 6, and 12 months after surgery, including fat mass evaluation by dual energy X-ray absorptiometry. WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry. RESULTS Fibrosis amount, distribution and collagen types (I, III, and VI) present distinct characteristics in lean and obese subjects and with WAT depots localization (subcutaneous or omental). Obese subjects had more total fibrosis in oWAT and had more pericellular fibrosis around adipocytes than lean subjects in both depots. Macrophages and mastocytes were highly represented in fibrotic bundles in oWAT, whereas scWAT was more frequently characterized by hypocellular fibrosis. The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = −0.30, P = 0.02), and with triglyceride levels (R = −0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05). Importantly, scWAT fibrosis correlated negatively with fat mass loss measured at the three time points after surgery. CONCLUSIONS Our data suggest differential clinical consequences of fibrosis in human WAT. In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

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Transgenerational Actions of Environmental Compounds on Reproductive Disease and Identification of Epigenetic Biomarkers of Ancestral Exposures

Mohan Manikkam, Carlos Guerrero-Bosagna, Rebecca Tracey … (2012)

Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1–F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Journal ID (iso-abbrev): Environ. Health Perspect

Journal ID (publisher-id): EHP

Title: Environmental Health Perspectives

Publisher: National Institute of Environmental Health Sciences

ISSN (Print): 0091-6765

ISSN (Electronic): 1552-9924

Publication date (Electronic): 05 December 2012

Publication date (Print): February 2013

Volume: 121

Issue: 2

Pages: 162-169

Affiliations

[1 ]Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA

[2 ]BioSimulation Consulting Inc., Newark, Delaware, USA

[3 ]Département de santé environnementale et santé au travail, Université de Montréal, Montréal, Québec, Canada

[4 ]INSERM UMR-S 747, Paris, France

[5 ]Université Paris Descartes, Centre Universitaire des Saints-Pères, Paris, France

[6 ]Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France

[7 ]Université Paris 13, Sorbonne Paris Cité, INSERM U698, Bobigny, France

[8 ]ONIRIS, USC 2013 INRA, LABERCA, Atlanpole-La Chantrerie, Nantes, France

[9 ]INSERM, U872, Nutriomique équipe 7, Paris, France

[10 ]Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris, France

[11 ]Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département Nutrition et Endocrinologie, Paris, France

[12 ]CRNH-Ile de France, Paris, France

[13 ]National Cancer Institute, and

[14 ]National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA

Author notes

Address correspondence to R. Barouki, Université Paris Descartes, INSERM UMRS 747, Centre Universitaire des Saints-Pères, 45 rue des Saints Pères, 75270 Paris, Cedex 06, France. Telephone: 33 (0)1 42 86 20 75. E-mail: robert.barouki@ 123456parisdescartes.fr

Article

Publisher ID: ehp.1205485

DOI: 10.1289/ehp.1205485

PMC ID: 3569688

PubMed ID: 23221922

SO-VID: b6abc377-8f98-4c10-9c61-1b6b0300504b

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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, properly cited.

Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants

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Most cited references 89

Rapid DNA methylation changes after exposure to traffic particles.

Fibrosis in Human Adipose Tissue: Composition, Distribution, and Link With Lipid Metabolism and Fat Mass Loss

Transgenerational Actions of Environmental Compounds on Reproductive Disease and Identification of Epigenetic Biomarkers of Ancestral Exposures

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