Evidence map›Paper›PMID 37354909›Full record

ArticleCell chemical biology2023

NREP contributes to development of NAFLD by regulating one-carbon metabolism in primary human hepatocytes.

Dario F De Jesus, Tomohiko Kimura, Manoj K Gupta, Rohit N Kulkarni

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2023. 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
0.9field-weighted citation impact, top 25% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. 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

4 authors at 1 institution in 1 country.

Dario F De JesusIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, and Harvard Medical School, Boston, MA, USA.
Tomohiko KimuraIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, and Harvard Medical School, Boston, MA, USA.
Manoj K GuptaIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, and Harvard Medical School, Boston, MA, USA.
Rohit N KulkarniIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, and Harvard Medical School, Boston, MA, USA. Electronic address: rohit.kulkarni@joslin.harvard.edu.
Joslin Diabetes Center · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Role of IGF-1 and Insulin Receptors Beta-Cell SurvivalR01DK067536 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 2004 to 2026
$8.0M
Interplay Between SERPINB1 and TLR2/TLR4 in Beta Cell RegenerationR01DK117639 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ARVAN, PETER, KULKARNI, ROHIT N. · 2019 to 2023
$3.0M
Role of SerpinB1 in beta cell growthR01DK103215 · NIDDK · JOSLIN DIABETES CENTER · PI KULKARNI, ROHIT N. · 2014 to 2018
$2.6M
NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK067536NIDDK NIH HHS R01 DK103215NIDDK NIH HHS R01 DK117639
6 · The paper itself

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. We recently discovered that neuronal regeneration-related protein (NREP/P311), an epigenetically regulated gene reprogrammed by parental metabolic syndrome, is downregulated in human NAFLD. To investigate the impact of NREP insufficiency, we used RNA-sequencing, lipidomics, and antibody microarrays on primary human hepatocytes. NREP knockdown induced transcriptomic remodeling that overlapped with key pathways impacted in human steatosis and steatohepatitis. Additionally, we observed enrichment of pathways involving phosphatidylinositol signaling and one-carbon metabolism. Lipidomics analyses also revealed an increase in cholesterol esters and triglycerides and decreased phosphatidylcholine levels in NREP-deficient hepatocytes. Signalomics identified calcium signaling as a potential mediator of NREP insufficiency's effects. Our results, together with the encouraging observation that several single nucleotide polymorphisms (SNPs) spanning the NREP locus are associated with metabolic traits, provide a strong rationale for targeting hepatic NREP to improve NAFLD pathophysiology.

Indexed as

Non-alcoholic Fatty Liver DiseaseCarbonHepatocytesHumansLipid MetabolismLiverCarbonCalcium signalingNAFLDNeuronal regeneration-related proteinNonalcoholic fatty liver diseaseNREPOne-carbon metabolismPhosphatidylinositol signalingSteatosis

Identifiers

PMID37354909
PMCPMC10529627
OpenAlexW4381850315

What OpenQuestion holds

Textmetadata
LicenceTDM
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.