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Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance
BACKGROUND: Despite a strong statistical correlation between dietary aflatoxin B1 (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative. This issue is important because of emerging interest in reduction of human aflatoxin exposure to diminish the prevalence and complicatio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506701/ https://www.ncbi.nlm.nih.gov/pubmed/25938735 http://dx.doi.org/10.1038/pr.2015.84 |
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author | Knipstein, Brittany Huang, Jiansheng Barr, Emily Sossenheimer, Philip Dietzen, Dennis Egner, Patricia A. Groopman, John D. Rudnick, David A. |
author_facet | Knipstein, Brittany Huang, Jiansheng Barr, Emily Sossenheimer, Philip Dietzen, Dennis Egner, Patricia A. Groopman, John D. Rudnick, David A. |
author_sort | Knipstein, Brittany |
collection | PubMed |
description | BACKGROUND: Despite a strong statistical correlation between dietary aflatoxin B1 (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative. This issue is important because of emerging interest in reduction of human aflatoxin exposure to diminish the prevalence and complications of stunting. Pediatric liver diseases cause growth impairment, and AFB1 is hepatotoxic. Thus, liver injury might mediate AFB1-associated growth impairment. We have developed a rat model of dietary AFB1-induced stunting to investigate these questions. METHODS: Newly-weaned rats were given AFB1-supplemented- or control-diets from age 3-9 weeks, and then euthanized for serum- and tissue-collection. Food intake and weight were serially assessed, with tibial-length determined at the experimental endpoint. Serum AFB1-adducts, hepatic gene and protein expression, and liver injury markers were quantified using established methodologies. RESULTS: AFB1-albumin adducts correlated with dietary toxin contamination, but such contamination did not affect food consumption. AFB1-exposed animals exhibited dose-dependent wasting and stunting, liver pathology, and suppression of hepatic targets of growth hormone (GH) signaling, but did not display increased mortality. CONCLUSION: These data establish toxin-dependent liver injury and hepatic GH-resistance as candidate mechanisms by which AFB1-exposure causes growth impairment in this mammalian model. Interrogation of modifiers of stunting using this model could guide interventions in at-risk and affected children. |
format | Online Article Text |
id | pubmed-4506701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45067012016-01-31 Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance Knipstein, Brittany Huang, Jiansheng Barr, Emily Sossenheimer, Philip Dietzen, Dennis Egner, Patricia A. Groopman, John D. Rudnick, David A. Pediatr Res Article BACKGROUND: Despite a strong statistical correlation between dietary aflatoxin B1 (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative. This issue is important because of emerging interest in reduction of human aflatoxin exposure to diminish the prevalence and complications of stunting. Pediatric liver diseases cause growth impairment, and AFB1 is hepatotoxic. Thus, liver injury might mediate AFB1-associated growth impairment. We have developed a rat model of dietary AFB1-induced stunting to investigate these questions. METHODS: Newly-weaned rats were given AFB1-supplemented- or control-diets from age 3-9 weeks, and then euthanized for serum- and tissue-collection. Food intake and weight were serially assessed, with tibial-length determined at the experimental endpoint. Serum AFB1-adducts, hepatic gene and protein expression, and liver injury markers were quantified using established methodologies. RESULTS: AFB1-albumin adducts correlated with dietary toxin contamination, but such contamination did not affect food consumption. AFB1-exposed animals exhibited dose-dependent wasting and stunting, liver pathology, and suppression of hepatic targets of growth hormone (GH) signaling, but did not display increased mortality. CONCLUSION: These data establish toxin-dependent liver injury and hepatic GH-resistance as candidate mechanisms by which AFB1-exposure causes growth impairment in this mammalian model. Interrogation of modifiers of stunting using this model could guide interventions in at-risk and affected children. 2015-05-04 2015-08 /pmc/articles/PMC4506701/ /pubmed/25938735 http://dx.doi.org/10.1038/pr.2015.84 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Knipstein, Brittany Huang, Jiansheng Barr, Emily Sossenheimer, Philip Dietzen, Dennis Egner, Patricia A. Groopman, John D. Rudnick, David A. Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance |
title | Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance |
title_full | Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance |
title_fullStr | Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance |
title_full_unstemmed | Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance |
title_short | Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance |
title_sort | dietary aflatoxin-induced stunting in a novel rat model: evidence for toxin-induced liver injury and hepatic growth hormone resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506701/ https://www.ncbi.nlm.nih.gov/pubmed/25938735 http://dx.doi.org/10.1038/pr.2015.84 |
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