Pubertal Exposure to the Endocrine Disruptor mono-2-ethylhexyl Ester at Body Burden Level Caused Cholesterol Imbalance in Mice

Environ Pollut. 2019 Jan;244:657-666. doi: 10.1016/j.envpol.2018.08.091. Epub 2018 Sep 20.

Abstract

Metabolic disturbance is the prerequisite to developing metabolic disease. An increasing number of reports have shown that exposure to environmental endocrine-disrupting chemicals (EDCs) can cause metabolic syndrome and may be related to metabolic disease. However, the potential mechanism of EDC-related lipid metabolism disruption in the endocrine organs (especially gut microbiome) during pubertal exposure remains elusive at the body burden level. We observed that male mice fed with 0.05 mg/kg b.w. MEHP under a high-fat diet caused enhancement in the fat mass, total cholesterol, high- and low-density lipoprotein cholesterol. MEHP intake induced a significant shift in microbiota composition, including the relative abundance of Firmicutes and reduction of Verrucomicrobia. Statistical analysis showed a positive correlation between several bacterial taxa and cholesterol body burden. Also, MEHP intake induced adipocyte hypertrophy and cholesterol overloading, which sense cholesterol synthesis genes such as Srebp2 and Hmgcr. That caused adipocyte dysfunction. Finally, cholesterol deposition and transportation was imbalance in the mice liver. Conclusively, by targeting the endocrine organs, EDCs would increase the risk of cholesterol burden even at a low concentration when coupled with a high-fat diet during pubertal period in male mice.

Keywords: Body burden level; Cholesterol accumulation; Gut microbiome; MEHP.

MeSH terms

  • Adipocytes / pathology
  • Animals
  • Body Burden
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood*
  • Diet, High-Fat
  • Endocrine Disruptors / toxicity*
  • Firmicutes / growth & development
  • Gastrointestinal Microbiome / drug effects*
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Lipid Metabolism / drug effects*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phthalic Acids / toxicity*
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Verrucomicrobia / growth & development

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Endocrine Disruptors
  • Phthalic Acids
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 2
  • mono(2-methoxyethyl) phthalate
  • Hydroxymethylglutaryl CoA Reductases