Pulmonary exposure to diesel exhaust particles enhances fatty change of the liver in obese diabetic mice

Makoto Tomaru, Hirohisa Takano, Ken Ichiro Inoue, Rie Yanagisawa, Naomi Osakabe, Akiko Yasuda, Akinori Shimada, Yoji Kato, Hiroshi Uematsu

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38 Citations (Scopus)


In epidemiological studies, exposure to ambient particulate matter (PM) has been reported to be positively associated with mortality in subjects with diabetes mellitus. Diesel exhaust particles (DEP) are major constituents of atmospheric PM. However, there is no experimental evidence for the relation of DEP to diabetes mellitus and its complications. We investigated the effects of DEP inoculated intratracheally on diabetic changes and nonalcoholic fatty liver disease (NAFLD) in diabetic obese and control mice. db/db mice and the corresponding nondiabetic db/+m mice received exposure to vehicle or DEP every two weeks. Animals were examined with biochemistry, histology, and immunohistochemistry for hexanoyl-lysine (HEL) in the liver. In the db/+m mice, pulmonary exposure to DEP did not increase levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) compared to that to vehicle. In the db/db mice, however, the exposure to DEP increased the levels of AST and ALT compared to that to vehicle. Only in the db/db mice, DEP enhanced the magnitude of steatosis and formation of HEL, a marker of oxidative stress, in the liver compared to vehicle. These results suggest that pulmonary exposure to DEP, PM, enhances steatosis in the liver of obese diabetic subjects possibly via enhanced oxidative stress.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalInternational Journal of Molecular Medicine
Issue number1
Publication statusPublished - 2007 Jan
Externally publishedYes


  • Cytochrome P450
  • Diesel exhaust particles
  • Nonalcoholic fatty liver disease
  • Particulate matter
  • Reactive oxygen species

ASJC Scopus subject areas

  • Genetics


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