Evidence map›Paper›PMID 41145601›Full record

ArticleScientific reports2025

Nardilysin in adipocyte regulates insulin sensitivity via HIF1α and PPARγ.

Shintaro Matsuda, Mikiko Ohno, Kiyoto Nishi, Shinya Ikeda, Hirotaka Iwasaki, Taiki Eifuku, Yoshinori Hiraoka, Takeshi Kimura, Koh Ono, Eiichiro Nishi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Nardilysin regulatesBiochemistry and biophysics reports · 2026
    Article
  2. Article
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

10 authors.

Shintaro MatsudaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo- ku, Kyoto, 606-8507, Japan.
Mikiko OhnoDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo- ku, Kyoto, 606-8507, Japan. moono@belle.shiga-med.ac.jp.
Kiyoto NishiDepartment of Pharmacology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Shinya IkedaDepartment of Pharmacology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Hirotaka IwasakiDepartment of Pharmacology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Taiki EifukuDepartment of Pharmacology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Yoshinori HiraokaDivision of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, Hyogo, 650-8586, Japan.
Takeshi KimuraDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo- ku, Kyoto, 606-8507, Japan.
Koh OnoDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo- ku, Kyoto, 606-8507, Japan.
Eiichiro NishiDepartment of Pharmacology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan. enishi@belle.shiga-med.ac.jp.

Funding

Japan Society for the Promotion of Science 20K22936Japan Society for the Promotion of Science 23K07550Japan Society for the Promotion of Science 23K07966Japan Society for the Promotion of Science 25K02686
6 · The paper itself

Abstract

Obesity is a critical global health issue and a major risk factor for type 2 diabetes mellitus (T2DM). However, molecular mechanism by which obesity leads to T2DM has not been fully elucidated. Here, we investigated the role of adipocyte nardilysin (NRDC) in insulin sensitivity using adipocyte-specific NRDC-knockout mice (Adipo-KO). Despite no difference in body weight, Adipo-KO demonstrated enhanced glucose tolerance and insulin sensitivity exclusively under high fat diet (HFD) conditions. Epididymal white adipose tissue (eWAT) in Adipo-KO showed the decreased crown-like structures and F4/80-positive cells. Consistently, insulin-stimulated Akt phosphorylation was elevated in the eWAT of HFD-fed Adipo-KO and 3T3-L1 adipocytes with NRDC knockdown. In addition, NRDC knockdown led to a decrease in cellular oxygen consumption rate and hypoxia-induced HIF1α expression in 3T3-L1 adipocytes. The augmented Akt phosphorylation by NRDC knockdown was reversed by daprodustat, which stabilizes HIF1α, suggesting that the effect of NRDC on insulin sensitivity is mediated by HIF1α. Upstream analysis of the differentially expressed genes (DEGs) in NRDC knockdown 3T3-L1 adipocytes revealed that PPARγ is enriched in the promoters of the DEGs. We also confirmed the complex formation of NRDC and PPARγ. In conclusion, NRDC in adipocyte regulates insulin sensitivity through HIF1α and PPARγ.

Indexed as

AdipocytesHypoxia-Inducible Factor 1, alpha SubunitInsulin ResistanceMetalloendopeptidasesPPAR gamma3T3-L1 CellsAdipose Tissue, WhiteAnimalsDiet, High-FatMaleMiceMice, Inbred C57BLMice, KnockoutObesityPhosphorylationProto-Oncogene Proteins c-aktHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitMetalloendopeptidasesnardilysinPPAR gammaProto-Oncogene Proteins c-aktAdipocyteHIF1αInsulin sensitivityNardilysin (NRDC)Oxygen consumptionPPARγ

Identifiers

PMID41145601
PMCPMC12559285

What OpenQuestion holds

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Registered trials

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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.