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Toxicological function of adipose tissue: focus on persistent organic pollutants.

La Merrill M, Emond C, Kim MJ, Antignac JP, Le Bizec B, Clément K, Birnbaum LS, Barouki R - Environ. Health Perspect. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.

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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Related in: MedlinePlus

Major signaling mechanisms involved in the effects of DL POPs on AT. Abbreviations: ER, estrogen receptor; RAR, retinoic acid receptor. Most, if not all, of the effects of DL compounds are mediated by the AhR. Only genomic effects are shown. The AhR could directly regulate target genes as a heterodimer with ARNT. Several interactions with transcription factors or nuclear receptors that have been described are shown here. POPs could either trigger these interactions or disrupt existing interactions between the AhR and other signaling factors.
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f3: Major signaling mechanisms involved in the effects of DL POPs on AT. Abbreviations: ER, estrogen receptor; RAR, retinoic acid receptor. Most, if not all, of the effects of DL compounds are mediated by the AhR. Only genomic effects are shown. The AhR could directly regulate target genes as a heterodimer with ARNT. Several interactions with transcription factors or nuclear receptors that have been described are shown here. POPs could either trigger these interactions or disrupt existing interactions between the AhR and other signaling factors.

Mentions: The mechanisms of DL chemical regulation of inflammation are complex and may depend on the system that is studied. Both anti-inflammatory and proinflammatory effects have been described. Because of the endogenous role of the AhR in the regulation of immunity, exogenous AhR ligands could either mimic or disrupt these pathways thereby influencing the regulation of inflammatory gene expression (Esser et al. 2009) (Figure 3). In addition, complex interactions between the AhR and critical transcription factors are involved in the regulation of inflammation, such as nuclear factor of kappa light polypeptide gene enhancer in B cells (NFκB) (Tian 2009; Vondracek et al. 2011). These interactions can also be observed in the absence of xenobiotics. For instance, the AhR forms a complex with signal transducer and activator of transcription 1 (STAT1) and NFκB to negatively regulate the innate inflammatory response even in the absence of an exogenous ligand (Kimura et al. 2009) (Figure 3). The interactions of the AhR with nuclear factor, erythroid derived 2, like 2 (NFE2L2) signaling could also account for its regulation of inflammation both in adipocytes and in other cells (Haarmann-Stemmann et al. 2012; Shin et al. 2007). The AhR and its ligands clearly modulate the inflammatory response. These effects could be due to the perturbation of an endogenous function of this receptor, as well as to additional effects triggered by xenobiotic activation.


Toxicological function of adipose tissue: focus on persistent organic pollutants.

La Merrill M, Emond C, Kim MJ, Antignac JP, Le Bizec B, Clément K, Birnbaum LS, Barouki R - Environ. Health Perspect. (2012)

Major signaling mechanisms involved in the effects of DL POPs on AT. Abbreviations: ER, estrogen receptor; RAR, retinoic acid receptor. Most, if not all, of the effects of DL compounds are mediated by the AhR. Only genomic effects are shown. The AhR could directly regulate target genes as a heterodimer with ARNT. Several interactions with transcription factors or nuclear receptors that have been described are shown here. POPs could either trigger these interactions or disrupt existing interactions between the AhR and other signaling factors.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569688&req=5

f3: Major signaling mechanisms involved in the effects of DL POPs on AT. Abbreviations: ER, estrogen receptor; RAR, retinoic acid receptor. Most, if not all, of the effects of DL compounds are mediated by the AhR. Only genomic effects are shown. The AhR could directly regulate target genes as a heterodimer with ARNT. Several interactions with transcription factors or nuclear receptors that have been described are shown here. POPs could either trigger these interactions or disrupt existing interactions between the AhR and other signaling factors.
Mentions: The mechanisms of DL chemical regulation of inflammation are complex and may depend on the system that is studied. Both anti-inflammatory and proinflammatory effects have been described. Because of the endogenous role of the AhR in the regulation of immunity, exogenous AhR ligands could either mimic or disrupt these pathways thereby influencing the regulation of inflammatory gene expression (Esser et al. 2009) (Figure 3). In addition, complex interactions between the AhR and critical transcription factors are involved in the regulation of inflammation, such as nuclear factor of kappa light polypeptide gene enhancer in B cells (NFκB) (Tian 2009; Vondracek et al. 2011). These interactions can also be observed in the absence of xenobiotics. For instance, the AhR forms a complex with signal transducer and activator of transcription 1 (STAT1) and NFκB to negatively regulate the innate inflammatory response even in the absence of an exogenous ligand (Kimura et al. 2009) (Figure 3). The interactions of the AhR with nuclear factor, erythroid derived 2, like 2 (NFE2L2) signaling could also account for its regulation of inflammation both in adipocytes and in other cells (Haarmann-Stemmann et al. 2012; Shin et al. 2007). The AhR and its ligands clearly modulate the inflammatory response. These effects could be due to the perturbation of an endogenous function of this receptor, as well as to additional effects triggered by xenobiotic activation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.

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.

Show MeSH
Related in: MedlinePlus