90ae943a71b696fe7a8299c7cc28cf0a blsf-19-00010-v2.pdf f3db075a5f05c1970637adfaf9a8929941e24492 blsf-19-00010-v2.pdf 4bf59b968352a8f92942b58016707eb0232f47a2f312ea1b8821d7ca00be566b blsf-19-00010-v2.pdf Title: Obesity, Impaired Glucose Metabolism and Hepatic Histopathological Damage in 3xTg-AD Mice at DifferentStages of Disease Compared to Mice with Normal Aging "2279 Subject: 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/genderperspective Author: Clara Pérez-Gozalbo and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Jun 19 04:15:53 2023 CEST ModDate: Mon Jun 19 04:17:51 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 2 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 212762 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 FJMEJE+VnURWPalladioL Type 1 Custom yes yes no 15 0 PQZUAO+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 KUSTCF+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 TZMXPD+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 CKUQXN+CMSY10 Type 1 Builtin yes yes no 32 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-20 02:15:04 CET RepresentationInformation: blsf-19-00010-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-19 10:19:16 CET Size: 212762 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 91 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Info: Title: Obesity, Impaired Glucose Metabolism and Hepatic Histopathological Damage in 3xTg-AD Mice at DifferentStages of Disease Compared to Mice with Normal Aging "2279 Author: Clara Pérez-Gozalbo and Lydia Giménez-Llort Subject: 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/genderperspective Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Jun 19 04:15:53 CEST 2023 ModDate: Mon Jun 19 04:17:51 CEST 2023 ID: 0xfd5b35445ac3a0a6479a3749fd72092f, 0xfd5b35445ac3a0a6479a3749fd72092f Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: CKUQXN+CMSY10 FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: CKUQXN+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: PQZUAO+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 134 FontDescriptor: FontName: PQZUAO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: KUSTCF+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 233 FontDescriptor: FontName: KUSTCF+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: BTFGED+VnURWPalladioL-Bold FontSubset: true FirstChar: 178 LastChar: 178 FontDescriptor: FontName: BTFGED+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: TZMXPD+URWPalladioL-Ital FontSubset: true FirstChar: 46 LastChar: 117 FontDescriptor: FontName: TZMXPD+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FJMEJE+VnURWPalladioL FontSubset: true FirstChar: 177 LastChar: 226 FontDescriptor: FontName: FJMEJE+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 75, 299, 152, 308 Annotation: Subtype: Link Rect: 34, 288, 116, 296 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 167, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 279, 639, 290, 653 Annotation: Subtype: Link Rect: 240, 553, 356, 563 Annotation: Subtype: Link Rect: 536, 219, 560, 230 Annotation: Subtype: Link Rect: 165, 207, 393, 218 Annotation: Subtype: Link Rect: 148, 17, 301, 28 Annotation: Subtype: Link Rect: 423, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 396, 87, 415 Page: Sequence: 2 Checksum: 778b9cfe Type: CRC32 Checksum: 90ae943a71b696fe7a8299c7cc28cf0a Type: MD5 Checksum: f3db075a5f05c1970637adfaf9a8929941e24492 Type: SHA-1 Checksum: 4bf59b968352a8f92942b58016707eb0232f47a2f312ea1b8821d7ca00be566b Type: SHA-256