Evidence map›Paper›PMID 32029232›Full record

ArticleMolecular metabolism2020

SWI/SNF complex subunit BAF60a represses hepatic ureagenesis through a crosstalk between YB-1 and PGC-1α.

Wenxiang Zhang, Zhewen Dong, Mengyi Xu, Shiyao Zhang, Chang Liu, Siyu Chen

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

Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. CPS1: Looking at an ancient enzyme in a modern light.Molecular genetics and metabolism · 2020
    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

6 authors at 1 institution in 1 country.

Wenxiang ZhangState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
Zhewen DongState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
Mengyi XuState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
Shiyao ZhangState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
Chang LiuState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; State key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, 211198, China. Electronic address: changliu@cpu.edu.cn.
Siyu ChenState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; State key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, 211198, China. Electronic address: siyuchen@cpu.edu.cn.
China Pharmaceutical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveUreagenesis predominantly occurs in the liver and functions to remove ammonia, and the dysregulation of ureagenesis leads to the development of hyperammonemia. Recent studies have shown that ureagenesis is under the control of nutrient signals, but the mechanism remains elusive. Therefore, intensive investigation of the molecular mechanism underlying ureagenesis will shed some light on the pathology of metabolic diseases related to ammonia imbalance.

methodsMice were fasted for 24 h or fed a high-fat diet (HFD) for 16 weeks. For human evaluation, we obtained a public data set including 41 obese patients with and without hepatic steatosis. We analyzed the expression levels of hepatic BAF60a under different nutrient status. The impact of BAF60a on ureagenesis and hyperammonemia was assessed by using gain- and loss-of-function strategies. The molecular chaperons mediating the effects of BAF60a on ureagenesis were validated by molecular biological strategies.

resultsBAF60a was induced in the liver of both fasted and HFD-fed mice and was positively correlated with body mass index in obese patients. Liver-specific overexpression of BAF60a inhibited hepatic ureagenesis, leading to the increase of serum ammonia levels. Mechanistically, BAF60a repressed the transcription of Cps1, a rate-limiting enzyme, through interaction with Y-box protein 1 (YB-1) and by switching the chromatin structure of Cps1 promoter into an inhibitory state. More importantly, in response to different nutrient status, PGC-1α (as a transcriptional coactivator) and YB-1 competitively bound to BAF60a, thus selectively regulating hepatic fatty acid β-oxidation and ureagenesis.

conclusionThe BAF60a-YB-1 axis represses hepatic ureagenesis, thereby contributing to hyperammonemia under overnutrient status. Therefore, hepatic BAF60a may be a novel therapeutic target for the treatment of overnutrient-induced urea cycle disorders and their associated diseases.

Indexed as

AnimalsChromosomal Proteins, Non-HistoneLiverMaleMiceMice, Inbred C57BLPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaTranscription FactorsUreaChromosomal Proteins, Non-HistonePeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseSmarcd1 protein, mouseTranscription FactorsUreaYbx1 protein, mouseBAF60aHyperammonemiaNutrient signalsUrea cycleYB-1

Identifiers

PMID32029232
PMCPMC6953711
OpenAlexW2995954169

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.