Evidence map›Paper›PMID 42711484›Full record

ArticleNature metabolism2026

Pentose phosphate pathway-derived NADPH facilitates physiological hypertrophy and alleviates ischemia-reperfusion injury in the heart.

Dan Wu, Tao Chen, Xin Dong, Haoqi Li, Zijie Cheng, Huimin Li, Yufan Chao, Fangling Li, Yun Yin, Fujun Guo and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Dan Wu *Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Tao Chen *Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resources, Chinese Academy of Science, Northwest Institute of Plateau Biology, Xining, China.
Xin Dong *Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.ORCID http://orcid.org/0000-0003-3709-0655
Haoqi LiShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Zijie ChengShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Huimin LiDepartment of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Yufan ChaoShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Fangling LiShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Yun YinDepartment of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Fujun GuoShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Xinran XuShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Yuxuan ZhangShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Kun NingShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Xiaoqing FuShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Yuemin BianShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.ORCID http://orcid.org/0000-0002-5845-772X
Fenfen MaDepartment of Pharmaceutics, School of Pharmacy, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
Julia RitterhoffDivision of Molecular and Translational Cardiology, Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany.
Wang WangMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
Qingxun HuShanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China. qingxh@shu.edu.cn.ORCID http://orcid.org/0000-0001-9288-6491

Funding

American Heart Association (American Heart Association, Inc.) 18EIA33900041, 25TPA1473092National Natural Science Foundation of China (National Science Foundation of China) 82100405Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 22ZR1456900
6 · The paper itself

Abstract

Exercise promotes physiological cardiomyocyte growth and protects against ischaemia-reperfusion (IR) injury in the heart. The molecular mechanism by which exercise benefits cardiac metabolism and function remains largely unknown. Here, using a genetically encoded fluorescent sensor, we show that exercise increases cytosolic, but not mitochondrial, NADPH levels in cardiomyocytes. This effect is mediated by activation of the pentose phosphate pathway (PPP). Inhibition of PPP activity or depletion of cytosolic NADPH attenuates exercise-induced heart hypertrophy in mice. We observe that NADPH promotes cardiomyocyte growth by inhibiting HDAC3/C/EBPβ pathways. Moreover, exercise-activated PPP/NADPH pathway suppresses acute IR injury and preserves heart function 4 weeks after IR. Among 310 tested Tibetan compounds, the spermidine derivative lyciumspermidine-0527 directly activates the rate-limiting PPP enzyme glucose-6-phosphate dehydrogenase, elevates intracellular NADPH levels and alleviates IR injury. Altogether, these results show that PPP-derived NADPH is a critical metabolic checkpoint that regulates exercise-induced physiological cardiomyocyte growth and protects against IR-induced heart injury.

Indexed as

CardiomegalyMyocardial Reperfusion InjuryNADPPentose Phosphate PathwayAnimalsMaleMiceMice, Inbred C57BLMyocytes, CardiacPhysical Conditioning, AnimalNADP

Identifiers

PMID42711484

What Socratic holds

Textmetadata
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.