Mechanisms of action, chemical characteristics, and model systems of obesogens

Abstract

There is increasing evidence for the role of environmental endocrine disrupting contaminants, coined obesogens, in exacerbating the rising obesity epidemic. Obesogens can be found in everyday items ranging from pesticides to food packaging. Although research shows that obesogens can have effects on adipocyte size, phenotype, metabolic activity, and hormone levels, much remains unknown about these chemicals. This review will discuss what is currently known about the mechanisms of obesogens, including expression of the PPARs, hormone interference, and inflammation. Strategies for identifying obesogenic chemicals and their mechanisms through chemical characteristics and model systems will also be discussed. Ultimately, research should focus on improving models to discern precise mechanisms of obesogenic action and to test therapeutics targeting these mechanisms.

Ecotoxicological Characterization of Type C Killer Whales From Terra Nova Bay (Ross Sea, Antarctica): Molecular Biomarkers, Legacy, and Emerging Persistent Organic Contaminants

“…Since the ligand-binding domain of whale PPARγ is the same as in other cetacean species, similar responses are expected also in killer whales (Lühmann et al, 2020). The PPARα mRNA levels can be modulated by the exposure to POPs and perfluorinated alkyl acids (PFAAs) compounds, and the activation of the receptor, in turn, promotes the transcription of genes responsible for energy metabolism and regulation of lipids (Kurtz et al, 2019;Griffin et al, 2020). The highest PPARα mRNA levels were found in the female KW011 and the lowest in KW002.…”

Prenatal Exposure to Mixtures of Phthalates, Parabens, and Other Phenols and Obesity in Five-Year-Olds in the CHAMACOS Cohort

“…Childhood fast food intake may also be a poor proxy for mothers' prenatal fast-food intake (e.g., children may eat more fast food than their parents did). Though the obesogenic mechanisms of these chemicals are not completely understood, several biological pathways could plausibly mediate the observed relationships [10]. Several phthalates, particularly monoester metabolites, and parabens are known to modulate the activity of peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ, nuclear receptors that regulate adipocyte differentiation and lipid metabolism [13,52,53].…”

“…Toxicological and epidemiological evidence has raised concern about these chemicals' endocrine-disrupting and possibly obesogenic effects [8]. Many phthalates, parabens, and phenols appear to cross the placenta [9] and may disrupt pathways of endocrine signaling and inflammatory responses [10], possibly through changes to fetal epigenetic mechanisms [11,12] and/or action on peroxisome proliferator-activated receptors [13].…”

Obesogens: How They Are Identified and Molecular Mechanisms Underlying Their Action

“…This class of EDCs was denoted as metabolism disrupting chemicals (MDCs) [reviewed in (26,27)]. Many chemical obesogens have been identified and numerous reviews have been written about them in recent years (22)(23)(24)28). The total number of obesogens is currently unknown because no systematic attempt has been undertaken to identify them.…”