Evidence map›Paper›PMID 34314389›Full record

ArticleJCI insight2021

Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1.

Yang Cao, Lingyi Tang, Kang Du, Kitt Paraiso, Qiushi Sun, Zhengxia Liu, Xiaolong Ye, Yuan Fang, Fang Yuan, Hank Chen and 12 more

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

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. 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

22 authors at 3 institutions in 2 countries.

Yang CaoDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Lingyi TangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Kang DuDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Kitt ParaisoDepartment of Developmental & Cell Biology, UCI, Irvine, California, USA.
Qiushi SunDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Zhengxia LiuDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Xiaolong YeDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Yuan FangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Fang YuanDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Hank ChenDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Yumay ChenDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Xiaorong WangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Clinton YuDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Ira L BlitzDepartment of Developmental & Cell Biology, UCI, Irvine, California, USA.
Ping H WangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Lan HuangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
Haibo ChengAffiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Xiang LuDepartment of Geriatrics, Sir Run Run Hospital of Nanjing Medical University, Nanjing, China.
Ken Wy ChoDepartment of Developmental & Cell Biology, UCI, Irvine, California, USA.
Marcus SeldinDepartment of Biological Chemistry, UCI, Irvine, California, USA.
Zhuyuan FangAffiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Qin YangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, California, USA.
University of California, Irvine · USNanjing University of Chinese Medicine · CNNanjing Medical University · CN

Funding

Proteomics of the Proteasome Interacting NetworksR01GM074830 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUANG, LAN · 2005 to 2022
$6.1M
Epigenetic Regulation of Mitochondrial Homeostasis and Energy MetabolismR01DK121146 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI Qin Yang · 2019 to 2026
$3.5M
Zygotic Genome Activation by Maternal Transcription Factors and Epigenetic ModifiersR35GM139617 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Ken W.Y. Cho · 2021 to 2026
$2.6M
Nicotinamide N-methyltransferase is a novel regulator of energy expenditureR01DK100385 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI YANG, QIN · 2014 to 2018
$1.7M
Mechanisms of Foxh1 pioneer factor action during mesendoderm developmentR01GM126395 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHO, KEN W.Y. · 2017 to 2020
$1.6M
Structural dynamics and function of the COP9 signalosomeR01GM130144 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUANG, LAN · 2018 to 2021
$1.2M
NIDDK NIH HHS R01 DK100385NIDDK NIH HHS R01 DK121146NIGMS NIH HHS R01 GM074830NIGMS NIH HHS R01 GM126395NIGMS NIH HHS R01 GM130144NIGMS NIH HHS R35 GM139617
6 · The paper itself

Abstract

Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than 1000 nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes remain to be fully elucidated. Here, we show that histone demethylase LSD1 KO from adult mouse liver (LSD1-LKO) reduces the expression of one-third of all nuclear-encoded mitochondrial genes and decreases mitochondrial biogenesis and function. LSD1-modulated histone methylation epigenetically regulates nuclear-encoded mitochondrial genes. Furthermore, LSD1 regulates gene expression and protein methylation of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), which controls the final step of NAD+ synthesis and limits NAD+ availability in the nucleus. Lsd1 KO reduces NAD+-dependent SIRT1 and SIRT7 deacetylase activity, leading to hyperacetylation and hypofunctioning of GABPβ and PGC-1α, the major transcriptional factor/cofactor for nuclear-encoded mitochondrial genes. Despite the reduced mitochondrial function in the liver, LSD1-LKO mice are protected from diet-induced hepatic steatosis and glucose intolerance, partially due to induction of hepatokine FGF21. Thus, LSD1 orchestrates a core regulatory network involving epigenetic modifications and NAD+ synthesis to control mitochondrial function and hepatokine production.

Indexed as

Gene Expression RegulationAnimalsCells, CulturedEpigenesis, GeneticFatty LiverFibroblast Growth FactorsGenes, MitochondrialHistone DemethylasesLiverMiceRNASignal TransductionFgf22 protein, mouseFibroblast Growth FactorsHistone DemethylasesKDM1a protein, mouseRNADiabetesEndocrinologyObesity

Identifiers

PMID34314389
PMCPMC8492328
OpenAlexW3184186616

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.