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Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Understanding gender-associated bias in aging and obesity-driven metabolic derangements has been hindered by the inability to model severe obesity in female mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Here, using chow- or high fat diet (HFD)-feeding regimens at standard (T<jats:sub>S<\/jats:sub>) and thermoneutral (T<jats:sub>N<\/jats:sub>) 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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<jats:sub>S<\/jats:sub>, resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under T<jats:sub>S<\/jats:sub> housing conditions only aged, but not young, HFD fed female mice developed obesity. At T<jats:sub>N<\/jats:sub> 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<jats:sub>reg<\/jats:sub>) 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41387-021-00157-0","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T11:02:58Z","timestamp":1623063778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner"],"prefix":"10.1038","volume":"11","author":[{"given":"Maria E.","family":"Moreno-Fernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishakha","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci E.","family":"Stankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarren R.","family":"Oates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-801X","authenticated-orcid":false,"given":"Jessica R.","family":"Doll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4617-2564","authenticated-orcid":false,"given":"Michelle S. 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