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Prevention of N‐nitrosodiethylamine (NDEA) ‐ mediated liver and brain degeneration with PPAR agonists or dietary soy
Author(s) -
Ramirez Teresa,
Van Stephanie P.,
Longato Lisa,
Tong Ming,
Nguyen QuynhGiao L.,
Monte Suzanne M.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1116.5
Subject(s) - agonist , insulin resistance , steatohepatitis , neurodegeneration , ppar agonist , medicine , endocrinology , liver x receptor , fatty liver , insulin , chemistry , receptor , nuclear receptor , biochemistry , disease , transcription factor , gene
Human nitrosamine exposures occur through use and consumption of tobacco and processed foods. In addition, to malignancies, nitrosamines cause degenerative diseases, including type 2 diabetes, non‐alcoholic steatohepatitis, and neurodegeneration, all of which are epidemic and linked to insulin and IGF resistance. We hypothesize that nitrosamine‐mediated liver and brain degeneration may be abated with insulin sensitizer drugs, e.g. PPAR agonists, or dietary soy, which contains anti‐oxidant and insulin sensitizer components. We exposed rats to NDEA or vehicle, and treated them with vehicle, a PPAR‐δ agonist, or dietary soy. NDEA exposure impaired spatial learning and memory, and caused striking steatohepatitis and neurodegeneration with insulin/IGF resistance in liver and brain. Dietary soy, to a greater extent than PPAR‐δ agonist treatment of NDEA exposed rats, restored liver and brain histology, and enhanced expression of genes (qRT‐PCR) and proteins (multiplex ELISAs) that mediate insulin/IGF signaling in liver and brain. These studies demonstrate that long‐term toxic and degenerative effects of NDEA in liver and brain can be prevented by either treatment with a PPAR agonist or dietary soy. Research was funded by AA‐11431, AA‐12908, and AA‐16126 from the National Institutes of Health.