Evidence map›Paper›PMID 40123006›Full record

ArticleCell death and differentiation2025

NAT10-mediated N4-acetylcytidine modification in KLF9 mRNA promotes adipogenesis.

Xinxing Wan, Linghao Wang, Md Asaduzzaman Khan, Lin Peng, Xiaoying Sun, Xuan Yi, Zhouqi Wang, Ke Chen

Abstract read
In one paragraph

Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. NAT10-Mediated ac4C Modification of circANKRD12 Reprograms the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. The NAT10/acCell communication and signaling : CCS · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. 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

8 authors.

Xinxing WanDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China.ORCID http://orcid.org/0000-0002-6617-0331
Linghao WangDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China.ORCID http://orcid.org/0009-0003-1772-8030
Md Asaduzzaman KhanDepartment of Biochemistry and Microbiology, School of Health & Life Sciences, North South University, Dhaka, Bangladesh.ORCID http://orcid.org/0000-0001-7851-0500
Lin PengDepartment of Nephrology, The First Hospital of Changsha, Changsha, Hunan, PR China.ORCID http://orcid.org/0000-0003-0463-4556
Xiaoying SunDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China.ORCID http://orcid.org/0009-0007-5560-2446
Xuan YiDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China.ORCID http://orcid.org/0009-0003-8009-3883
Zhouqi WangDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China.ORCID http://orcid.org/0009-0006-1298-6913
Ke ChenDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China. chenke520@yeah.net.ORCID http://orcid.org/0000-0003-2882-9358

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysfunctional adipogenesis is a major contributor of obesity. N-acetyltransferase 10 (NAT10) plays a crucial role in regulating N4-acetylcysteine (ac4C) modification in tRNA, 18SrRNA, and mRNA. As the sole "writer" in the ac4C modification process, NAT10 enhances mRNA stability and translation efficiency. There are few reports on the relationship between NAT10 and adipogenesis, as well as obesity. Our study revealed a significant upregulation of NAT10 in adipose tissues of obese individuals and high-fat diet-fed mice. Furthermore, our findings revealed that the overexpression of NAT10 promotes adipogenesis, while its silencing inhibits adipogenesis in both human adipose tissue-derived stem cells (hADSCs) and 3T3-L1 cells. These results indicate the intimate relationship between NAT10 and obesity. After silencing mouse NAT10 (mNAT10), we identified 30 genes that exhibited both hypo-ac4C modification and downregulation in their expression, utilizing a combined approach of acRIP-sequencing (acRIP-seq) and RNA-sequencing (RNA-seq). Among these genes, we validated KLF9 as a target of NAT10 through acRIP-PCR. KLF9, a pivotal transcription factor that positively regulates adipogenesis. Our findings showed that NAT10 enhances the stability of KLF9 mRNA and further activates the CEBPA/B-PPARG pathway. Furthermore, a dual-luciferase reporter assay demonstrated that NAT10 can bind to three motifs of mouse KLF9 and one motif of human KLF9. In vivo studies revealed that adipose tissue-targeted mouse AAV-NAT10 (AAV-shRNA-mNAT10) inhibits adipose tissue expansion in mice. Additionally, Remodelin, a specific NAT10 inhibitor, significantly reduced body weight, adipocyte size, and adipose tissue expansion in high-fat diet-fed mice by inhibiting KLF9 mRNA ac4C modification. These findings provide novel insights and experimental evidence of the prevention and treatment of obesity, highlighting NAT10 and its downstream targets as potential therapeutic targets.

Indexed as

AcetyltransferasesAdipogenesisCytidineKruppel-Like Transcription FactorsRNA, Messenger3T3-L1 CellsAdipose TissueAnimalsDiet, High-FatHumansMaleMiceMice, Inbred C57BLObesityAcetyltransferasesCytidineKLF9 protein, humanKruppel-Like Transcription FactorsRNA, Messenger

Identifiers

PMID40123006
PMCPMC12432206

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.