Evidence map›Paper›PMID 41421649›Full record

ArticleJournal of sport and health science2025

Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging mice.

Lian Wang, Liwei Mao, Danlin Zhu, Ke Li, Haoyang Gao, Muge Zhou, Jiabin Wu, Dan Yang, Ze Wang, Wenhong Wang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of sport and health science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
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

14 authors.

Lian WangShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Liwei MaoShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Danlin ZhuShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
Ke LiShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
Haoyang GaoShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
Muge ZhouShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Rehabilitation Center, Children's Hospital of Fudan University, Shanghai 201102, China.
Jiabin WuShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
Dan YangShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
Ze WangShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
Wenhong WangShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Research Institute for Biology and Medicine, Hunan University of Medicine, Huaihua 418000, China.
Yifan GuoShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Yingying XuShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Physical Education, Henan Sport University, Zhengzhou 450044, China.
Peijie ChenShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. Electronic address: chenpeijie@sus.edu.cn.
Weihua XiaoShanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. Electronic address: xiaoweihua@sus.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAging is a major contributor to cognitive decline and neurodegeneration, yet effective interventions to counteract aging-related neuronal dysfunction remain limited. β-hydroxybutyrate (β-HB), a ketone body elevated during fasting or aerobic exercise, functions as both an energy substrate and a signaling metabolite.

methodsWe assessed the effects of exercise-induced and exogenously supplemented β-HB on cognitive performance in aging mice. To examine the role of endogenous β-HB metabolism, we used 3-hydroxybutyrate dehydrogenase 1 (BDH1) knockout mice. In vitro, we investigated the impact of G protein-coupled receptor 109A (GPR109A) knockdown on β-HB-mediated activation of peroxisome proliferator-activated receptor gamma (PPARγ) and downstream pathways.

resultsExercise elevated circulating β-HB levels and improved cognitive outcomes in aging mice. Exogenous β-HB supplementation mimicked these benefits. Loss of BDH1 impaired endogenous β-HB production and attenuated both exercise- and β-HB-induced cognitive improvements. In vitro, GPR109A knockdown suppressed β-HB-driven activation of PPARγ and downstream neuroprotective pathways linked to inflammation and oxidative stress.

conclusionThese findings identify the β-HB/GPR109A-PPARγ axis as a key mediator of exercise-induced cognitive enhancement in aging. β-HB emerges as a potential therapeutic candidate to mitigate brain aging and cognitive decline.

Indexed as

BDH1ExerciseGPR109APPARγβ-hydroxybutyrate

Identifiers

PMID41421649
PMCPMC13351753

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.