Evidence map›Paper›PMID 33558457›Full record

ArticleSignal transduction and targeted therapy2021

Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis.

Sha Xu, Hui Tao, Wei Cao, Li Cao, Yan Lin, Shi-Min Zhao, Wei Xu, Jing Cao, Jian-Yuan Zhao

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 4 pooled it
16.4field-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

87 citing papers in PubMed, 4 syntheses or guidelines pooled it, 184 citations in OpenAlex.

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27 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

9 authors at 4 institutions in 1 country.

Sha Xu *Zhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of NPFPC, and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, China.
Hui Tao *Department of Cardiothoracic Surgery, Second Hospital of Anhui Medical University, and Cardiovascular Research Center, Anhui Medical University, 230601, Hefei, China.
Wei Cao *Department of Cardiothoracic Surgery, Second Hospital of Anhui Medical University, and Cardiovascular Research Center, Anhui Medical University, 230601, Hefei, China.
Li CaoZhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of NPFPC, and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, China.ORCID 0000-0003-3391-0513
Yan LinZhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of NPFPC, and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, China.
Shi-Min ZhaoZhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of NPFPC, and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, China.
Wei XuZhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of NPFPC, and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, China.
Jing CaoDepartment of Anatomy and Neuroscience Research Institute, School of Basic Medical Sciences, Zhengzhou University, 450001, Zhengzhou, China.
Jian-Yuan ZhaoZhongshan Hospital of Fudan University, Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences, Key Laboratory of Reproduction Regulation of NPFPC, and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, China. zhaojy@fudan.edu.cn.ORCID 0000-0001-9861-0330
Sichuan University · CNAnhui Medical University · CNZhongshan Hospital · CNZhengzhou University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In addition to their use in relieving the symptoms of various diseases, ketogenic diets (KDs) have also been adopted by healthy individuals to prevent being overweight. Herein, we reported that prolonged KD exposure induced cardiac fibrosis. In rats, KD or frequent deep fasting decreased mitochondrial biogenesis, reduced cell respiration, and increased cardiomyocyte apoptosis and cardiac fibrosis. Mechanistically, increased levels of the ketone body β-hydroxybutyrate (β-OHB), an HDAC2 inhibitor, promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription. This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis, leading to cardiomyocyte apoptosis and cardiac fibrosis. Exogenous β-OHB administration mimicked the effects of a KD in rats. Notably, increased β-OHB levels and SIRT7 expression, decreased mitochondrial biogenesis, and increased cardiac fibrosis were detected in human atrial fibrillation heart tissues. Our results highlighted the unknown detrimental effects of KDs and provided insights into strategies for preventing cardiac fibrosis in patients for whom KDs are medically necessary.

Indexed as

3-Hydroxybutyric AcidAcetylationAnimalsApoptosisDiet, KetogenicDisease Models, AnimalFastingFibrosisGene Expression RegulationHistone Deacetylase 2HistonesHumansKetone BodiesMaleMyocytes, CardiacOrganelle Biogenesis3-Hydroxybutyric AcidHdac2 protein, ratHistone Deacetylase 2HistonesKetone BodiesSIRT7 protein, ratSirtuins

Identifiers

PMID33558457
PMCPMC7870678
OpenAlexW3129189546

What OpenQuestion 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 OpenQuestion graph.