Exposure to air pollution interacts with obesogenic nutrition to induce tissue-specific response patterns

Michal Pardo, Yael Kuperman, Liron Levin, Assaf Rudich, Yulia Haim, James J. Schauer, Alon Chen, Yinon Rudich

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2. Obesogenic nutrition and air pollution activate inflammation and other stress response pathway in a tissue specific manner, potentially reflecting tissue-specific regulation of DNA methyltransferases.

Original languageEnglish
Pages (from-to)532-543
Number of pages12
JournalEnvironmental Pollution
StatePublished - 1 Aug 2018


  • Air pollution
  • Inflammation
  • Intra-tracheal instillation
  • Lungs
  • Methyltransferases
  • Nrf2 transcription factor
  • Obesogenic nutrition
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology
  • Pollution
  • Health, Toxicology and Mutagenesis


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