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Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner

BACKGROUND: Understanding gender-associated bias in aging and obesity-driven metabolic derangements has been hindered by the inability to model severe obesity in female mice. METHODS: Here, using chow- or high fat diet (HFD)-feeding regimens at standard (T(S)) and thermoneutral (T(N)) housing temper...

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Autores principales: Moreno-Fernandez, Maria E., Sharma, Vishakha, Stankiewicz, Traci E., Oates, Jarren R., Doll, Jessica R., Damen, Michelle S. M. A., Almanan, Maha A. T. A., Chougnet, Claire A., Hildeman, David A., Divanovic, Senad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184786/
https://www.ncbi.nlm.nih.gov/pubmed/34099626
http://dx.doi.org/10.1038/s41387-021-00157-0
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author Moreno-Fernandez, Maria E.
Sharma, Vishakha
Stankiewicz, Traci E.
Oates, Jarren R.
Doll, Jessica R.
Damen, Michelle S. M. A.
Almanan, Maha A. T. A.
Chougnet, Claire A.
Hildeman, David A.
Divanovic, Senad
author_facet Moreno-Fernandez, Maria E.
Sharma, Vishakha
Stankiewicz, Traci E.
Oates, Jarren R.
Doll, Jessica R.
Damen, Michelle S. M. A.
Almanan, Maha A. T. A.
Chougnet, Claire A.
Hildeman, David A.
Divanovic, Senad
author_sort Moreno-Fernandez, Maria E.
collection PubMed
description BACKGROUND: Understanding gender-associated bias in aging and obesity-driven metabolic derangements has been hindered by the inability to model severe obesity in female mice. METHODS: Here, using chow- or high fat diet (HFD)-feeding regimens at standard (T(S)) and thermoneutral (T(N)) housing temperatures, the latter to model obesity in female mice, we examined the impact of gender and aging on obesity-associated metabolic derangements and immune responsiveness. Analysis included quantification of: (i) weight gain and adiposity; (ii) the development and severity of glucose dysmetabolism and non-alcoholic fatty liver disease (NAFLD); and (iii) induction of inflammatory pathways related to metabolic dysfunction. RESULTS: We show that under chow diet feeding regimen, aging was accompanied by increased body weight and white adipose tissue (WAT) expansion in a gender independent manner. HFD feeding regimen in aged, compared to young, male mice at T(S), resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under T(S) housing conditions only aged, but not young, HFD fed female mice developed obesity. At T(N) however, both young and aged HFD fed female mice developed severe obesity. Independent of gender or housing conditions, aging attenuated the severity of metabolic derangements in HFD-fed obese mice. Tempered severity of metabolic derangements in aged mice was associated with increased splenic frequency of regulatory T (T(reg)) cells, Type I regulatory (Tr1)-like cells and circulating IL-10 levels and decreased vigor of HFD-driven induction of inflammatory pathways in adipose and liver tissues. CONCLUSION: Our findings suggest that aging-associated altered immunological profile and inflammatory vigor may play a dominant role in the attenuation of obesogenic diet-driven metabolic dysfunction.
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spelling pubmed-81847862021-06-09 Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner Moreno-Fernandez, Maria E. Sharma, Vishakha Stankiewicz, Traci E. Oates, Jarren R. Doll, Jessica R. Damen, Michelle S. M. A. Almanan, Maha A. T. A. Chougnet, Claire A. Hildeman, David A. Divanovic, Senad Nutr Diabetes Article BACKGROUND: Understanding gender-associated bias in aging and obesity-driven metabolic derangements has been hindered by the inability to model severe obesity in female mice. METHODS: Here, using chow- or high fat diet (HFD)-feeding regimens at standard (T(S)) and thermoneutral (T(N)) housing temperatures, the latter to model obesity in female mice, we examined the impact of gender and aging on obesity-associated metabolic derangements and immune responsiveness. Analysis included quantification of: (i) weight gain and adiposity; (ii) the development and severity of glucose dysmetabolism and non-alcoholic fatty liver disease (NAFLD); and (iii) induction of inflammatory pathways related to metabolic dysfunction. RESULTS: We show that under chow diet feeding regimen, aging was accompanied by increased body weight and white adipose tissue (WAT) expansion in a gender independent manner. HFD feeding regimen in aged, compared to young, male mice at T(S), resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under T(S) housing conditions only aged, but not young, HFD fed female mice developed obesity. At T(N) however, both young and aged HFD fed female mice developed severe obesity. Independent of gender or housing conditions, aging attenuated the severity of metabolic derangements in HFD-fed obese mice. Tempered severity of metabolic derangements in aged mice was associated with increased splenic frequency of regulatory T (T(reg)) cells, Type I regulatory (Tr1)-like cells and circulating IL-10 levels and decreased vigor of HFD-driven induction of inflammatory pathways in adipose and liver tissues. CONCLUSION: Our findings suggest that aging-associated altered immunological profile and inflammatory vigor may play a dominant role in the attenuation of obesogenic diet-driven metabolic dysfunction. Nature Publishing Group UK 2021-06-07 /pmc/articles/PMC8184786/ /pubmed/34099626 http://dx.doi.org/10.1038/s41387-021-00157-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Moreno-Fernandez, Maria E.
Sharma, Vishakha
Stankiewicz, Traci E.
Oates, Jarren R.
Doll, Jessica R.
Damen, Michelle S. M. A.
Almanan, Maha A. T. A.
Chougnet, Claire A.
Hildeman, David A.
Divanovic, Senad
Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
title Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
title_full Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
title_fullStr Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
title_full_unstemmed Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
title_short Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
title_sort aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184786/
https://www.ncbi.nlm.nih.gov/pubmed/34099626
http://dx.doi.org/10.1038/s41387-021-00157-0
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