Age‐related changes to adipose tissue and peripheral neuropathy in genetically diverse HET3 mice differ by sex and are not mitigated by rapamycin longevity treatment
Article Swipe
Jake W. Willows
,
Morganne Robinson
,
Zahra Alshahal
,
Samantha K. Morrison
,
Gargi Mishra
,
Harrison Cyr
,
Magdalena Blaszkiewicz
,
Gilian Gunsch
,
Sabrina DiPietro
,
Emma Paradie
,
Benjamin Tero
,
Anne Harrington
,
Larisa Ryzhova
,
Lucy Liaw
,
Peter C. Reifsnyder
,
David E. Harrison
,
Kristy L. Townsend
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1111/acel.13784
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1111/acel.13784
Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabetes, and aging), total subcutaneous white adipose tissue (scWAT) innervation is decreased (‘adipose neuropathy’). With advanced age in the C57BL/6J mouse, small fiber peripheral nerve endings in adipose tissue die back, resulting in reduced contact with adipose‐resident blood vessels and other cells. This vascular neuropathy and parenchymal neuropathy together likely pose a physiological challenge for tissue function. In the current work, we used the genetically diverse HET3 mouse model to investigate the incidence of peripheral neuropathy and adipose tissue dysregulation across several ages in both male and female mice. We also investigated the anti‐aging treatment rapamycin, an mTOR inhibitor, as a means to prevent or reduce adipose neuropathy. We found that HET3 mice displayed a reduced neuropathy phenotype compared to inbred C56BL/6 J mice, indicating genetic contributions to this aging phenotype. Compared to female HET3 mice, male HET3 mice had worse neuropathic phenotypes by 62 weeks of age. Female HET3 mice appeared to have increased protection from neuropathy until advanced age (126 weeks), after reproductive senescence. We found that rapamycin overall had little impact on neuropathy measures, and actually worsened adipose tissue inflammation and fibrosis. Despite its success as a longevity treatment in mice, higher doses and longer delivery paradigms for rapamycin may lead to a disconnect between life span and beneficial health outcomes.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/acel.13784
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.13784
- OA Status
- gold
- Cited By
- 19
- References
- 92
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4321168780
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4321168780Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1111/acel.13784Digital Object Identifier
- Title
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Age‐related changes to adipose tissue and peripheral neuropathy in genetically diverse
HET3 mice differ by sex and are not mitigated by rapamycin longevity treatmentWork title - Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-02-16Full publication date if available
- Authors
-
Jake W. Willows, Morganne Robinson, Zahra Alshahal, Samantha K. Morrison, Gargi Mishra, Harrison Cyr, Magdalena Blaszkiewicz, Gilian Gunsch, Sabrina DiPietro, Emma Paradie, Benjamin Tero, Anne Harrington, Larisa Ryzhova, Lucy Liaw, Peter C. Reifsnyder, David E. Harrison, Kristy L. TownsendList of authors in order
- Landing page
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https://doi.org/10.1111/acel.13784Publisher landing page
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.13784Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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-
goldOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.13784Direct OA link when available
- Concepts
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Adipose tissue, Biology, Internal medicine, Endocrinology, White adipose tissue, Peripheral neuropathy, Diabetes mellitus, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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19Total citation count in OpenAlex
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2025: 5, 2024: 6, 2023: 8Per-year citation counts (last 5 years)
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92Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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