Obesogens.
OBJECTIVE
The environmental obesogen hypothesis postulates chemical pollutants that are able to promote obesity by altering homeostatic metabolic set-points, disrupting appetite controls, perturbing lipid homeostasis to promote adipocyte hypertrophy, or stimulating adipogenic pathways that enhance adipocyte hyperplasia during development or in adults. This review focuses on recent experimental advances for candidate obesogens that target nuclear hormone receptors when a direct link between exposure, modulation of transcriptional networks and adipogenic phenotypes can be rationalized.


RESULTS
Various endocrine disrupting chemicals can disrupt hormonal signaling relevant to adipose tissue biology. In this review, progress on one identified obesogen, the organotin tributyltin, will be outlined to highlight principles and novel insights into its high-affinity nuclear hormone receptor-mediated mechanism, its effects on adipocyte biology, its potential to promote long-term obesogenic changes and its epidemiological relevance. When appropriate, important results for other suspected obesogenic ligands, including bisphenol A, phthalates, polybrominated diphenyl ethers and perfluoro-compounds, will highlight corroborating principles.


CONCLUSIONS
These examples serve to provide perspective on the potential harm that man-made obesogenic pollutants pose to human health, focus attention on areas in which knowledge remains inadequate and prompt a re-evaluation of the causative risk factors driving the current changes in obesity rates.
Grün
Felix
F
Center for Complex Biological Systems, University of California Irvine, Irvine, California 92697-2280, USA. fgrun@uci.edu
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors / Q000378:metabolism* / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009765:Obesity / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists; D010636:Phenols / Q000378:metabolism / Q000633:toxicity; D010641:Phenotype; D010795:Phthalic Acids / Q000378:metabolism / Q000633:toxicity; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists; D014158:Transcription, Genetic / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000378:metabolism / Q000633:toxicity; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005466:Fluorocarbons; D055768:Halogenated Diphenyl Ethers; D047495:PPAR gamma; D010636:Phenols; D010795:Phthalic Acids; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D014220:Trialkyltin Compounds; C011559:tributyltin; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds