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High‐fat diet prevents the development of autoimmune diabetes in NOD mice
AIMS: Type 1 diabetes (T1D) has a strong genetic predisposition and requires an environmental trigger to initiate the beta‐cell autoimmune destruction. The rate of childhood obesity has risen in parallel to the proportion of T1D, suggesting high‐fat diet (HFD)/obesity as potential environmental trig...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490276/ https://www.ncbi.nlm.nih.gov/pubmed/34212475 http://dx.doi.org/10.1111/dom.14486 |
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author | Clark, Amy L. Yan, Zihan Chen, Sophia X. Shi, Victoria Kulkarni, Devesha H. Diwan, Abhinav Remedi, Maria S. |
author_facet | Clark, Amy L. Yan, Zihan Chen, Sophia X. Shi, Victoria Kulkarni, Devesha H. Diwan, Abhinav Remedi, Maria S. |
author_sort | Clark, Amy L. |
collection | PubMed |
description | AIMS: Type 1 diabetes (T1D) has a strong genetic predisposition and requires an environmental trigger to initiate the beta‐cell autoimmune destruction. The rate of childhood obesity has risen in parallel to the proportion of T1D, suggesting high‐fat diet (HFD)/obesity as potential environmental triggers for autoimmune diabetes. To explore this, non‐obese diabetic (NOD) mice were subjected to HFD and monitored for the development of diabetes, insulitis and beta‐cell stress. MATERIALS AND METHODS: Four‐week‐old female NOD mice were placed on HFD (HFD‐NOD) or standard chow‐diet. Blood glucose was monitored weekly up to 40 weeks of age, and glucose‐ and insulin‐tolerance tests performed at 4, 10 and 15 weeks. Pancreata and islets were analysed for insulin secretion, beta‐cell mass, inflammation, insulitis and endoplasmic reticulum stress markers. Immune cell levels were measured in islets and spleens. Stool microbiome was analysed at age 4, 8 and 25 weeks. RESULTS: At early ages, HFD‐NOD mice showed a significant increase in body weight, glucose intolerance and insulin resistance; but paradoxically, they were protected from developing diabetes. This was accompanied by increased insulin secretion and beta‐cell mass, decreased insulitis, increased splenic T‐regulatory cells and altered stool microbiome. CONCLUSIONS: This study shows that HFD protects NOD mice from autoimmune diabetes and preserves beta‐cell mass and function through alterations in gut microbiome, increased T‐regulatory cells and decreased insulitis. Further studies into the exact mechanism of HFD‐mediated prevention of diabetes in NOD mice could potentially lead to interventions to prevent or delay T1D development in humans. |
format | Online Article Text |
id | pubmed-8490276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-84902762022-10-14 High‐fat diet prevents the development of autoimmune diabetes in NOD mice Clark, Amy L. Yan, Zihan Chen, Sophia X. Shi, Victoria Kulkarni, Devesha H. Diwan, Abhinav Remedi, Maria S. Diabetes Obes Metab Original Articles AIMS: Type 1 diabetes (T1D) has a strong genetic predisposition and requires an environmental trigger to initiate the beta‐cell autoimmune destruction. The rate of childhood obesity has risen in parallel to the proportion of T1D, suggesting high‐fat diet (HFD)/obesity as potential environmental triggers for autoimmune diabetes. To explore this, non‐obese diabetic (NOD) mice were subjected to HFD and monitored for the development of diabetes, insulitis and beta‐cell stress. MATERIALS AND METHODS: Four‐week‐old female NOD mice were placed on HFD (HFD‐NOD) or standard chow‐diet. Blood glucose was monitored weekly up to 40 weeks of age, and glucose‐ and insulin‐tolerance tests performed at 4, 10 and 15 weeks. Pancreata and islets were analysed for insulin secretion, beta‐cell mass, inflammation, insulitis and endoplasmic reticulum stress markers. Immune cell levels were measured in islets and spleens. Stool microbiome was analysed at age 4, 8 and 25 weeks. RESULTS: At early ages, HFD‐NOD mice showed a significant increase in body weight, glucose intolerance and insulin resistance; but paradoxically, they were protected from developing diabetes. This was accompanied by increased insulin secretion and beta‐cell mass, decreased insulitis, increased splenic T‐regulatory cells and altered stool microbiome. CONCLUSIONS: This study shows that HFD protects NOD mice from autoimmune diabetes and preserves beta‐cell mass and function through alterations in gut microbiome, increased T‐regulatory cells and decreased insulitis. Further studies into the exact mechanism of HFD‐mediated prevention of diabetes in NOD mice could potentially lead to interventions to prevent or delay T1D development in humans. Blackwell Publishing Ltd 2021-08-02 2021-11 /pmc/articles/PMC8490276/ /pubmed/34212475 http://dx.doi.org/10.1111/dom.14486 Text en © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Clark, Amy L. Yan, Zihan Chen, Sophia X. Shi, Victoria Kulkarni, Devesha H. Diwan, Abhinav Remedi, Maria S. High‐fat diet prevents the development of autoimmune diabetes in NOD mice |
title | High‐fat diet prevents the development of autoimmune diabetes in NOD mice |
title_full | High‐fat diet prevents the development of autoimmune diabetes in NOD mice |
title_fullStr | High‐fat diet prevents the development of autoimmune diabetes in NOD mice |
title_full_unstemmed | High‐fat diet prevents the development of autoimmune diabetes in NOD mice |
title_short | High‐fat diet prevents the development of autoimmune diabetes in NOD mice |
title_sort | high‐fat diet prevents the development of autoimmune diabetes in nod mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490276/ https://www.ncbi.nlm.nih.gov/pubmed/34212475 http://dx.doi.org/10.1111/dom.14486 |
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