Evidence map›Paper›PMID 26100857›Full record

ArticleNature communications2015

A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism.

Yang Xu, Munaf Zalzala, Jiesi Xu, Yuanyuan Li, Liya Yin, Yanqiao Zhang

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed, 4 pooled it
7.3field-weighted citation impact, top 2% 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

158 citing papers in PubMed, 4 syntheses or guidelines pooled it, 267 citations in OpenAlex.

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98 more citing papers are in PubMed but not listed here.

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.

Yang XuDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA.
Munaf ZalzalaDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA.
Jiesi XuDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA.
Yuanyuan LiDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA.
Liya YinDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA.
Yanqiao ZhangDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA.ORCID 0000000218867775
Northeast Ohio Medical University · US

Funding

Mechanisms Underlying the Pathogenesis of Non-alcoholic Fatty Liver DiseaseR01DK102619 · NIDDK · UNIVERSITY OF ARIZONA · PI Yanqiao Zhang · 2015 to 2026
$4.0M
Regulation of Lipid and Lipoprotein Metabolism by Nuclear ReceptorsR01HL103227 · NHLBI · NORTHEAST OHIO MEDICAL UNIVERSITY · PI YIN, LIYA, ZHANG, YANQIAO · 2011 to 2019
$3.1M
Identification of Novel Genes/Pathways That Regulate Lipid and Glucose MetabolismR01DK095895 · NIDDK · NORTHEAST OHIO MEDICAL UNIVERSITY · PI ZHANG, YANQIAO · 2012 to 2015
$1.3M
Hepatocyte Nuclear Factor 4alpha and Lipid HomeostasisR15DK088733 · NIDDK · NORTHEAST OHIO MEDICAL UNIVERSITY · PI ZHANG, YANQIAO · 2010 to 2010
$462k
NHLBI NIH HHS R01 HL103227NHLBI NIH HHS R01HL103227NIDDK NIH HHS R01 DK095895NIDDK NIH HHS R01DK095895NIDDK NIH HHS R01 DK102619NIDDK NIH HHS R01DK102619NIDDK NIH HHS R15 DK088733NIDDK NIH HHS R15DK088733NLM NIH HHS HHSN276201200017CPHS HHS HHSN276201200017C
6 · The paper itself

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, but its underlying mechanism is poorly understood. Here we show that hepatocyte nuclear factor 4α (HNF4α), a liver-enriched nuclear hormone receptor, is markedly inhibited, whereas miR-34a is highly induced in patients with non-alcoholic steatohepatitis, diabetic mice and mice fed a high-fat diet. miR-34a is essential for HNF4α expression and regulates triglyceride accumulation in human and murine hepatocytes. miR-34a inhibits very low-density lipoprotein secretion and promotes liver steatosis and hypolipidemia in an HNF4α-dependent manner. As a result, increased miR-34a or reduced HNF4α expression in the liver attenuates the development of atherosclerosis in Apoe(-/-) or Ldlr(-/-) mice. These data indicate that the miR-34a-HNF4α pathway is activated under common conditions of metabolic stress and may have a role in the pathogenesis of NAFLD and in regulating plasma lipoprotein metabolism. Targeting this pathway may represent a novel approach for the treatment of NAFLD.

Indexed as

AnimalsApolipoproteins EAtherosclerosisDiabetes Mellitus, ExperimentalHepatocyte Nuclear Factor 4Hep G2 CellsHumansLipid MetabolismLipoproteinsLiverMice, KnockoutMicroRNAsMiddle AgedNon-alcoholic Fatty Liver DiseaseReceptors, LDLStress, PhysiologicalApolipoproteins EHepatocyte Nuclear Factor 4HNF4A protein, humanHnf4a protein, mouseLipoproteinsMicroRNAsMIRN34a microRNA, mouseMIRN34 microRNA, humanReceptors, LDLTriglycerides

Identifiers

PMID26100857
PMCPMC4479415
OpenAlexW2260144515

What OpenQuestion holds

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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.