Low-dose pollutant mixture triggers metabolic disturbances in female mice leading to common and specific features as compared to a high-fat diet

J Nutr Biochem. 2017 Jul;45:83-93. doi: 10.1016/j.jnutbio.2017.04.001. Epub 2017 Apr 8.

Abstract

Environmental pollutants are potential etiologic factors of obesity and diabetes that reach epidemic proportions worldwide. However, it is important to determine if pollutants could exert metabolic defects without directly inducing obesity. The metabolic disturbances triggered in nonobese mice lifelong exposed to a mixture of low-dose pollutants (2,3,7,8-tetrachlorodibenzo-p-dioxine, polychlorinated biphenyl 153, diethylhexyl-phthalate, and bisphenol A) were compared with changes provoked by a high-fat high-sucrose (HFHS) diet not containing the pollutant mixture. Interestingly, females exposed to pollutants exhibited modifications in lipid homeostasis including a significant increase of hepatic triglycerides but also distinct features from those observed in diet-induced obese mice. For example, they did not gain weight nor was glucose tolerance impacted. To get more insight, a transcriptomic analysis was performed in liver for comparison. We observed that in addition to the xenobiotic/drug metabolism pathway, analysis of the hepatic signature illustrated that the steroid/cholesterol, fatty acid/lipid and circadian clock metabolic pathways were targeted in response to pollutants as observed in the diet-induced obese mice. However, the specific sets of dysregulated annotated genes (>1300) did not overlap more than 40% between both challenges with some genes specifically altered only in response to pollutant exposure. Collectively, results show that pollutants and HFHS affect common metabolic pathways, but by different, albeit overlapping, mechanisms. This is highly relevant for understanding the synergistic effects between pollutants and the obesogenic diet reported in the literature.

Keywords: Cholesterol; Circadian clock; Dyslipidemia; Endocrine disruptors; Hepatic transcriptome; Metabolic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / toxicity
  • Circadian Clocks / drug effects
  • Circadian Clocks / genetics
  • Diet, High-Fat / adverse effects*
  • Duodenum / drug effects
  • Environmental Exposure / adverse effects
  • Environmental Pollutants / administration & dosage*
  • Environmental Pollutants / toxicity*
  • Fatty Acids / genetics
  • Fatty Acids / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Inactivation, Metabolic / genetics
  • Insulin Resistance
  • Liver / drug effects*
  • Liver / physiology
  • Mice, Inbred C57BL
  • Phenols / administration & dosage
  • Phenols / toxicity
  • Polychlorinated Dibenzodioxins / administration & dosage
  • Polychlorinated Dibenzodioxins / toxicity
  • Reproducibility of Results
  • Steroids / biosynthesis

Substances

  • Benzhydryl Compounds
  • Environmental Pollutants
  • Fatty Acids
  • Phenols
  • Polychlorinated Dibenzodioxins
  • Steroids
  • bisphenol A