Evidence map›Paper›PMID 35365608›Full record

ArticleNature communications2022

Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy.

Mingming Zhao, Haoran Wei, Chenze Li, Rui Zhan, Changjie Liu, Jianing Gao, Yaodong Yi, Xiao Cui, Wenxin Shan, Liang Ji and 12 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
12.6field-weighted citation impact, top 1% of its field
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

70 citing papers in PubMed, 97 citations in OpenAlex.

  1. Review
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  6. Vegetarian Dietary Patterns and Diet-Related Metabolites Are Associated With Kidney Function in the Adventist Health Study-2 Cohort.Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation · 2026
    Article
  7. Metabolic syndrome and a broken heart: trust your gut or risk your heart.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  8. Article
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  10. Article
  11. The Yin and Yang of copper in cardiovascular health and disease.Molecular and cellular biochemistry · 2026
    Review
  12. Role of Gut Microbiota in Diabetic HFpEF: Mechanisms and Therapeutic Implications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

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

22 authors at 9 institutions in 3 countries.

Mingming Zhao *Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
Haoran Wei *Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Chenze LiDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Rui ZhanThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
Changjie LiuThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
Jianing GaoThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
Yaodong YiLaboratory of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Xiao CuiDepartment of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Wenxin ShanThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
Liang JiThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
Bing PanThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
Si ChengBeijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, 100050, China.
Moshi SongState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.ORCID http://orcid.org/0000-0001-9929-8975
Haipeng SunDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Huidi JiangLaboratory of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Jun CaiFuwai Hospital, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Minerva T Garcia-BarrioCardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Y Eugene ChenCardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0003-2357-7825
Xiangbao MengState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.ORCID http://orcid.org/0000-0003-3418-9975
Erdan DongDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
Dao Wen WangDivision of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. dwwang@tjh.tjmu.edu.cn.ORCID http://orcid.org/0000-0002-9774-3980
Lemin ZhengThe Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China. zhengl@bjmu.edu.cn.ORCID http://orcid.org/0000-0003-4473-6936
Peking University · CNZhejiang University · CNCapital Medical University · CNTongji Hospital · CNUniversity of Michigan · USChinese Academy of Medical Sciences & Peking Union Medical College · CNChinese Academy of Sciences · CNShanghai Jiao Tong University · CNWuhan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n = 1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.

Indexed as

Gastrointestinal MicrobiomeAmino Acids, NeutralAnimalsCardiomegalyFatty AcidsHumansMiceProspective StudiesValerates5-aminovaleric acidAmino Acids, NeutralFatty AcidsN,N,N-trimethyl-5-aminovaleric acidValerates

Identifiers

PMID35365608
PMCPMC8976029
OpenAlexW4220961987

What Socratic holds

Textmetadata
LicenceCC BY
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.