Evidence map›Paper›PMID 40349321›Full record

ArticleThe Journal of physiology2026

A polygenetic rat model of divergent aerobic capacity reveals a liver-brain interaction impacting Alzheimer's disease-like phenotypes.

Colton R Lysaker, Benjamin A Kugler, Vivien Csikos, Cole J Birky, Caleb A Gilmore, Madi Wenger, Edziu Franczak, Xin Davis, Brittany M Hauger, Julie A Allen and 11 more

Abstract read
In one paragraph

Article in The Journal of physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Colton R LysakerDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Benjamin A KuglerDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0003-0822-7106
Vivien CsikosDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Cole J BirkyDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Caleb A GilmoreDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Madi WengerDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Edziu FranczakDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0002-0845-4002
Xin DavisDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0009-0006-9410-6560
Brittany M HaugerDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Julie A AllenDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Benjamin R TroutwineDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0002-1687-4736
Laura Gonzalez-DuranUniversity of Navarra, Pamplona, Spain.
Colin S McCoinDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Munish ChauhanHoglund Biomedical Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA.
Janna L HarrisHoglund Biomedical Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA.
Alexandria L FrazierKansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, USA.
Michelle K WinterKansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0002-8231-995X
Lauren G KochDepartment of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA.ORCID 0000-0002-2019-5939
Steven L BrittonDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
John P ThyfaultUniversity of Kansas Alzheimer's Disease Research Center, Kansas City, KS, USA.ORCID 0000-0001-7920-7466
Heather M WilkinsDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0003-4563-4544

Funding

Mentoring CoreP20GM103418 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SUSAN J. BROWN · 2012 to 2026
$63.0M
University of Kansas Alzheimer's Disease Research Center (KU ADRC)P30AG072973 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mohammad Haeri · 2021 to 2026
$25.3M
Using PCORnet to Expand the DS-CONNECT Cohort Through Healthcare System Recruitment, Incorporating Electronic Health Records, and Assessing Self-DeterminationU54HD090216 · NICHD · UNIVERSITY OF KANSAS LAWRENCE · PI BRADY, NANCY CAROLINE · 2016 to 2020
$6.2M
Kansas University Training Program in Neurological and Rehabilitation SciencesT32HD057850 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Jacob J. Sosnoff · 2009 to 2026
$3.4M
Divergence in Aerobic Capacity Drives Liver and Brain HealthR01DK121497 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI THYFAULT, JOHN P · 2019 to 2022
$2.2M
Multidisciplinary Research Training Program in Alzheimer's Disease and Related DisordersT32AG078114 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Sandra A Billinger, Eric Dennis Vidoni · 2022 to 2026
$1.2M
Relationship between Amyloid beta and BioenergeticsR00AG056600 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI WILKINS, HEATHER M. · 2020 to 2022
$747k
BLRD VA I01 BX002567NIA NIH HHS P30 AG072973NIA NIH HHS R00 AG056600NIA NIH HHS T32 AG078114NICHD NIH HHS T32 HD057850NICHD NIH HHS U54 HD090216NIDDK NIH HHS R01 DK121497NIGMS NIH HHS P20 GM103418
6 · The paper itself

Abstract

The interaction between liver and brain health is an emerging complex relationship implicated in Alzheimer's disease (AD). Divergence in aerobic capacity influences liver and brain health independently; however, whether these factors converge to influence AD risk is mechanistically unknown. Bile acid metabolism has been implicated as a link between liver and brain health and is modulated by aerobic capacity. Here, we examined rats selectively bred for high vs. low intrinsic aerobic capacity [high and low-capacity runner (HCR or LCR)] on indices of hepatic metabolism and brain health following a chronic low-fat, high-fat, or high-fat diet with bile acid sequestrant from 6 to 12 months of age. Pre- and post-diet measures included learning, memory, and brain volume metabolite levels. We additionally quantified brain and liver Aβ and proteins associated with Aβ production and clearance, as well as liver and brain mitochondrial energetics and liver bile acid species. We found that not only did aerobic capacity and diet influence mitochondrial function, but also it modified Aβ levels across the liver and brain. Additionally, aerobic capacity and diet altered bile acid profiles and brain hippocampal metabolite levels. The addition of bile acid sequestrant lowered brain Aβ levels in a sexually dimorphic manner. Aerobic capacity but not diet altered cognitive outcomes. Our results indicate that aerobic capacity and diet-induced liver health alterations modulate brain health with respect to metabolism and AD-like pathologies, whereas a stimulation of faecal bile acid loss could have positive effects on lowering brain Aβ. KEY POINTS: Aerobic capacity and diet-induced alterations to liver function alter liver bile acid species and faecal energy loss. Aerobic capacity and diet alter both brain and liver Aβ homeostasis. Aerobic capacity modulates brain and hippocampal volume in addition to brain metabolism. Aerobic capacity influences learning in middle-aged rats.

Indexed as

Alzheimer DiseaseBrainLiverPhysical Conditioning, AnimalAmyloid beta-PeptidesAnimalsBile Acids and SaltsDiet, High-FatDisease Models, AnimalFemaleMalePhenotypeRatsAmyloid beta-PeptidesBile Acids and SaltsAlzheimer's diseaseamyloid betabile acidsbrain volumefaecal energy losshippocampal volumelearningmitochondriaMRS

Identifiers

PMID40349321
PMCPMC13127301

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.