Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats
Abstract Background Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree to which the...
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BMC
2025-01-01
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| Series: | Immunity & Ageing |
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| Online Access: | https://doi.org/10.1186/s12979-024-00496-3 |
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| author | Michael J. Butler Stephanie M. Muscat Maria Elisa Caetano-Silva Akriti Shrestha Brigitte M. González Olmo Sabrina E. Mackey-Alfonso Nashali Massa Bryan D. Alvarez Jade A. Blackwell Menaz N. Bettes James W. DeMarsh Robert H. McCusker Jacob M. Allen Ruth M. Barrientos |
| author_facet | Michael J. Butler Stephanie M. Muscat Maria Elisa Caetano-Silva Akriti Shrestha Brigitte M. González Olmo Sabrina E. Mackey-Alfonso Nashali Massa Bryan D. Alvarez Jade A. Blackwell Menaz N. Bettes James W. DeMarsh Robert H. McCusker Jacob M. Allen Ruth M. Barrientos |
| author_sort | Michael J. Butler |
| collection | DOAJ |
| description | Abstract Background Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree to which these rapid inflammatory changes are unique to the brain is unknown. Moreover, deviations in gut microbiome composition have been associated with obesity and cognitive impairment, but how diet and aging interact to impact the gut microbiome, or how rapidly these changes occur, is less clear. Thus, our study investigated the impact of HFD after two distinct consumption durations: 3 months (to model diet-induced obesity) or 3 days (to detect the rapid changes occurring with HFD) on memory function, anxiety-like behavior, central and peripheral inflammation, and gut microbiome profile in young and aged rats. Results Our data indicated that both short-term and long-term HFD consumption impaired memory function and increased anxiety-like behavior in aged, but not young adult, rats. These behavioral changes were accompanied by pro- and anti-inflammatory cytokine dysregulation in the hippocampus and amygdala of aged HFD-fed rats at both time points. However, changes to fasting glucose, insulin, and inflammation in peripheral tissues such as the distal colon and visceral adipose tissue were increased in young and aged rats only after long-term, but not short-term, HFD consumption. Furthermore, while subtle HFD-induced changes to the gut microbiome did occur rapidly, robust age-specific effects were only present following long-term HFD consumption. Conclusions Overall, these data suggest that HFD-evoked neuroinflammation, memory impairment, and anxiety-like behavior in aging develop quicker than, and separately from the peripheral hallmarks of diet-induced obesity. |
| format | Article |
| id | doaj-art-c2926e4c0c7f4c91b87c77361ec10222 |
| institution | Kabale University |
| issn | 1742-4933 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Immunity & Ageing |
| spelling | doaj-art-c2926e4c0c7f4c91b87c77361ec102222025-01-05T12:46:12ZengBMCImmunity & Ageing1742-49332025-01-0122112110.1186/s12979-024-00496-3Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged ratsMichael J. Butler0Stephanie M. Muscat1Maria Elisa Caetano-Silva2Akriti Shrestha3Brigitte M. González Olmo4Sabrina E. Mackey-Alfonso5Nashali Massa6Bryan D. Alvarez7Jade A. Blackwell8Menaz N. Bettes9James W. DeMarsh10Robert H. McCusker11Jacob M. Allen12Ruth M. Barrientos13Institute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityDepartment of Health and Kinesiology, University of Illinois at Urbana-ChampaignDepartment of Health and Kinesiology, University of Illinois at Urbana-ChampaignInstitute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityInstitute for Behavioral Medicine Research, Ohio State UniversityDepartment of Health and Kinesiology, University of Illinois at Urbana-ChampaignDepartment of Health and Kinesiology, University of Illinois at Urbana-ChampaignInstitute for Behavioral Medicine Research, Ohio State UniversityAbstract Background Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree to which these rapid inflammatory changes are unique to the brain is unknown. Moreover, deviations in gut microbiome composition have been associated with obesity and cognitive impairment, but how diet and aging interact to impact the gut microbiome, or how rapidly these changes occur, is less clear. Thus, our study investigated the impact of HFD after two distinct consumption durations: 3 months (to model diet-induced obesity) or 3 days (to detect the rapid changes occurring with HFD) on memory function, anxiety-like behavior, central and peripheral inflammation, and gut microbiome profile in young and aged rats. Results Our data indicated that both short-term and long-term HFD consumption impaired memory function and increased anxiety-like behavior in aged, but not young adult, rats. These behavioral changes were accompanied by pro- and anti-inflammatory cytokine dysregulation in the hippocampus and amygdala of aged HFD-fed rats at both time points. However, changes to fasting glucose, insulin, and inflammation in peripheral tissues such as the distal colon and visceral adipose tissue were increased in young and aged rats only after long-term, but not short-term, HFD consumption. Furthermore, while subtle HFD-induced changes to the gut microbiome did occur rapidly, robust age-specific effects were only present following long-term HFD consumption. Conclusions Overall, these data suggest that HFD-evoked neuroinflammation, memory impairment, and anxiety-like behavior in aging develop quicker than, and separately from the peripheral hallmarks of diet-induced obesity.https://doi.org/10.1186/s12979-024-00496-3CytokinesHigh fat dietGut microbiome |
| spellingShingle | Michael J. Butler Stephanie M. Muscat Maria Elisa Caetano-Silva Akriti Shrestha Brigitte M. González Olmo Sabrina E. Mackey-Alfonso Nashali Massa Bryan D. Alvarez Jade A. Blackwell Menaz N. Bettes James W. DeMarsh Robert H. McCusker Jacob M. Allen Ruth M. Barrientos Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats Immunity & Ageing Cytokines High fat diet Gut microbiome |
| title | Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats |
| title_full | Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats |
| title_fullStr | Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats |
| title_full_unstemmed | Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats |
| title_short | Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats |
| title_sort | obesity associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats |
| topic | Cytokines High fat diet Gut microbiome |
| url | https://doi.org/10.1186/s12979-024-00496-3 |
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