Metabolic outcome of female mice exposed to a mixture of low-dose pollutants in a diet-induced obesity model

PLoS One. 2015 Apr 24;10(4):e0124015. doi: 10.1371/journal.pone.0124015. eCollection 2015.


Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic impact of food pollutants using a recently set up model in which mice are life-long fed a high-fat/high-sucrose diet (HFSD) with/without common food pollutants shown to exhibit metabolic disrupting activities. Specifically, this mixture comprised bisphenol A, dioxin, polychlorobiphenyl PCB153, and phthalate and was added in HFSD at doses resulting in mice exposure at the Tolerable Daily Intake dose range for each pollutant. We herein focused on the 7-week-old females which exhibited early signs of obesity upon HFSD feeding. We observed no signs of toxicity and no additional weight gain following exposure to the mixture but alleviated HFSD-induced glucose intolerance in the absence of alteration of gluconeogenesis and steatosis. It suggested that the observed metabolic improvement was more likely due to effects on muscle and/or adipose tissues rather than on the liver. Consistently, female mice exhibited enhanced lean/fat mass ratio and skeletal muscle insulin sensitivity. Moreover, expression levels of inflammatory markers were reduced in adipose tissue at 7 but enhanced at 12 weeks of age in agreement with the inverse alterations of glucose tolerance observed at these ages upon pollutant exposure in the HFSD-fed females. Collectively, these data suggest apparent biphasic effects of pollutants upon HFSD feeding along with obesity development. These effects were not observed in males and may depend on interactions between diet and pollutants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Body Weight
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Environmental Pollutants / adverse effects*
  • Fatty Acids / metabolism
  • Female
  • Gene Expression
  • Inflammation Mediators / metabolism
  • Liver / metabolism
  • Metabolome*
  • Metabolomics* / methods
  • Mice
  • Obesity / etiology*
  • Obesity / metabolism*
  • Oxidation-Reduction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism
  • Time Factors


  • Environmental Pollutants
  • Fatty Acids
  • Inflammation Mediators
  • RNA, Messenger
  • Sulfotransferases
  • estrone sulfotransferase

Grant support

The authors declare that this research project was supported by grants from the European Foundation of the Study of Diabetes (EFSD/Novo Nordisk, program 2011) and the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES; Programme National Environnement-Santé-Travail, EST-2010/2/2007). Emmanuel Labaronne is a recipient of “Région Rhône-Alpes”, France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.