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

Abstract 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 (TS) and thermoneutral (TN) housing tem...

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Main Authors: Maria E. Moreno-Fernandez, Vishakha Sharma, Traci E. Stankiewicz, Jarren R. Oates, Jessica R. Doll, Michelle S. M. A. Damen, Maha A. T. A. Almanan, Claire A. Chougnet, David A. Hildeman, Senad Divanovic
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Nutrition & Diabetes
Online Access:https://doi.org/10.1038/s41387-021-00157-0
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author Maria E. Moreno-Fernandez
Vishakha Sharma
Traci E. Stankiewicz
Jarren R. Oates
Jessica R. Doll
Michelle S. M. A. Damen
Maha A. T. A. Almanan
Claire A. Chougnet
David A. Hildeman
Senad Divanovic
author_facet Maria E. Moreno-Fernandez
Vishakha Sharma
Traci E. Stankiewicz
Jarren R. Oates
Jessica R. Doll
Michelle S. M. A. Damen
Maha A. T. A. Almanan
Claire A. Chougnet
David A. Hildeman
Senad Divanovic
author_sort Maria E. Moreno-Fernandez
collection DOAJ
description Abstract 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 (TS) and thermoneutral (TN) 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 TS, resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under TS housing conditions only aged, but not young, HFD fed female mice developed obesity. At TN 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 (Treg) 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 doaj.art-7d0c748d3a344ab1a14d117f2eb1e4a92022-12-21T21:58:52ZengNature Publishing GroupNutrition & Diabetes2044-40522021-06-0111111310.1038/s41387-021-00157-0Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent mannerMaria E. Moreno-Fernandez0Vishakha Sharma1Traci E. Stankiewicz2Jarren R. Oates3Jessica R. Doll4Michelle S. M. A. Damen5Maha A. T. A. Almanan6Claire A. Chougnet7David A. Hildeman8Senad Divanovic9Department of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineDepartment of Pediatrics, University of Cincinnati College of MedicineAbstract 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 (TS) and thermoneutral (TN) 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 TS, resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under TS housing conditions only aged, but not young, HFD fed female mice developed obesity. At TN 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 (Treg) 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.https://doi.org/10.1038/s41387-021-00157-0
spellingShingle Maria E. Moreno-Fernandez
Vishakha Sharma
Traci E. Stankiewicz
Jarren R. Oates
Jessica R. Doll
Michelle S. M. A. Damen
Maha A. T. A. Almanan
Claire A. Chougnet
David A. Hildeman
Senad Divanovic
Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
Nutrition & Diabetes
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
url https://doi.org/10.1038/s41387-021-00157-0
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