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Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity

PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD)...

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Autores principales: Hargrave, Aubrey, Courson, Justin A., Pham, Vanna, Landry, Paul, Magadi, Sri, Shankar, Pooja, Hanlon, Sam, Das, Apoorva, Rumbaut, Rolando E., Smith, C. Wayne, Burns, Alan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473521/
https://www.ncbi.nlm.nih.gov/pubmed/32886728
http://dx.doi.org/10.1371/journal.pone.0238750
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author Hargrave, Aubrey
Courson, Justin A.
Pham, Vanna
Landry, Paul
Magadi, Sri
Shankar, Pooja
Hanlon, Sam
Das, Apoorva
Rumbaut, Rolando E.
Smith, C. Wayne
Burns, Alan R.
author_facet Hargrave, Aubrey
Courson, Justin A.
Pham, Vanna
Landry, Paul
Magadi, Sri
Shankar, Pooja
Hanlon, Sam
Das, Apoorva
Rumbaut, Rolando E.
Smith, C. Wayne
Burns, Alan R.
author_sort Hargrave, Aubrey
collection PubMed
description PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5–15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. RESULTS: After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. CONCLUSION: In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention.
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spelling pubmed-74735212020-09-14 Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity Hargrave, Aubrey Courson, Justin A. Pham, Vanna Landry, Paul Magadi, Sri Shankar, Pooja Hanlon, Sam Das, Apoorva Rumbaut, Rolando E. Smith, C. Wayne Burns, Alan R. PLoS One Research Article PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5–15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. RESULTS: After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. CONCLUSION: In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention. Public Library of Science 2020-09-04 /pmc/articles/PMC7473521/ /pubmed/32886728 http://dx.doi.org/10.1371/journal.pone.0238750 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Hargrave, Aubrey
Courson, Justin A.
Pham, Vanna
Landry, Paul
Magadi, Sri
Shankar, Pooja
Hanlon, Sam
Das, Apoorva
Rumbaut, Rolando E.
Smith, C. Wayne
Burns, Alan R.
Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
title Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
title_full Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
title_fullStr Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
title_full_unstemmed Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
title_short Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
title_sort corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473521/
https://www.ncbi.nlm.nih.gov/pubmed/32886728
http://dx.doi.org/10.1371/journal.pone.0238750
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