Abstract
The crosstalk between obesity, diabetes, steatohepatitis, and dementia creates a controversial scenario when also studied using animal models. In the present work, this crosstalk was investigated in male and female 3xTg-AD mice for Alzheimer’s disease (AD) at different ages/stages and compared to sex- and age-matched counterparts with normal aging. The relevance of the genetic background and classical intrinsic factors (AD genotype and sex) were determined using a retrospective analysis of population data and an experimental design. Age/stage of disease was considered a source of stochastic and non-stochastic factors. Data from two different colonies of 3xTg-AD mice with distinct genetic backgrounds were analyzed to verify the functional interplay between the studied factors. Data from asymptomatic/prodromal to early/advanced stages of the disease were screened. Then, all factors’ relationships were studied in an experimental design using the same set of animals. The population data unveiled that the genetic background and sex effects were confirmed with regards to the variable body weight, with changes during disease development and progress. Sexual dimorphism was found as an important factor in glucose metabolism. Statistically significant differences in glucose tolerance and behavioral assessment (exploration, anxiety, and cognition in a two-days open-field paradigm) were found when all the factors were analyzed. In summary, the present study shows that all the studied factors should always be considered when assessing the outcome of the research interventions in the field because they have a distinct functional interplay through the process of normal and AD-pathological aging and from a gendered perspective.
Keywords:
obesity; glucose metabolism; liver; dementia; Alzheimer’s disease; aging; sex/gender perspective Supplementary Materials
The presentation material of this work are available online at https://www.mdpi.com/article/10.3390/IECBS2022-12938/s1.
Author Contributions
L.G.-L., conceptualization, methodology, supervision and writing; C.P.-G., methodology, data analysis and writing. Both authors revised and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.
Funding
The colonies were sustained by Fet-Open ArrestAD European Union’s Horizon 2020 research and innovation program under grant agreement No. 737390 to L.G.-L.; C.P.-G received the ‘Beca de col·laboració al Departament de Psiquiatria i Medicina Legal 2018’ from AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca) 2018 COLAB 00234 P.
Institutional Review Board Statement
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Departament de Medi Ambient I Habitatge, Generalitat de Catalunya (CEEAH 3588/DMAH 9452) the 8 March 2019.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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