Evidence map›Paper›PMID 23314846›Full record

ArticleDiabetologia2013

ER stress signalling through eIF2α and CHOP, but not IRE1α, attenuates adipogenesis in mice.

J Han, R Murthy, B Wood, B Song, S Wang, B Sun, H Malhi, R J Kaufman

Open access · greenAbstract read
In one paragraph

Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% 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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  6. Review
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  8. Review
  9. 1,25-dihydroxyvitamin DNutrition research and practice · 2024
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  11. Antiobesity Drug Discovery Research:Current drug targets · 2024
    Review
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  15. The Recent Advances in Molecular Diagnosis of Soft Tissue Tumors.International journal of molecular sciences · 2023
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

8 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

8 authors at 3 institutions in 1 country.

J HanDel E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037-1062, USA.
R Murthy
B Wood
B Song
S Wang
B Sun
H Malhi
R J Kaufman
University of Michigan–Ann Arbor · USOtsuka (United States) · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
TRANSGENIC MODELS FOR THE STUDY OF FACTOR V FUNCTIONP01HL057346 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SUN, HONGMIN · 1997 to 2013
$19.9M
Regulation of Factor VIII SecretionR01HL052173 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 1995 to 2014
$6.5M
Role of the Unfolded Protein Response in Beta CellR37DK042394 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 2007 to 2016
$4.9M
Regulation of ER stress-induced cell deathR01DK088227 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 2010 to 2014
$3.1M
Unfolded Protein Response in Glucose HomeostasisR01DK042394 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 2003 to 2006
$1.2M
Mechanisms of Liver InflammationK08DK097178 · NIDDK · MAYO CLINIC ROCHESTER · PI MALHI, HARMEET · 2012 to 2016
$730k
Alteration in protein interactions with proinsulin and insulin in type 2 diabetesR24DK093074 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI KAUFMAN, RANDAL J. · 2011 to 2011
$518k
NHLBI NIH HHS HL052173NHLBI NIH HHS HL057346NHLBI NIH HHS P01 HL057346NHLBI NIH HHS R01 HL052173NIDDK NIH HHS DK020572NIDDK NIH HHS DK042394NIDDK NIH HHS DK088227NIDDK NIH HHS DK093074NIDDK NIH HHS K08 DK097178NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P60 DK020572NIDDK NIH HHS R01 DK042394NIDDK NIH HHS R01 DK088227NIDDK NIH HHS R24 DK093074NIDDK NIH HHS R37 DK042394
6 · The paper itself

Abstract

aims/hypothesisAlthough obesity is associated with endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in adipose tissue, it is not known how UPR signalling affects adipogenesis. To test whether signalling through protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 alpha (PERK/eIF2α) or inositol-requiring enzyme 1 alpha/X-box binding protein 1 (IRE1α/XBP1) is required for adipogenesis, we studied the role of UPR signalling in adipocyte differentiation in vitro and in vivo in mice.

methodsThe role of UPR signalling in adipogenesis was investigated using 3T3-L1 cells and primary mouse embryonic fibroblasts (MEFs) by activation or inhibition of PERK-mediated phosphorylation of the eIF2α- and IRE1α-mediated splicing of Xbp1 mRNA. Body weight change, fat mass composition and adipocyte number and size were measured in wild-type and genetically engineered mice fed a control or high-fat diet (HFD).

resultsER stress repressed adipocyte differentiation in 3T3-L1 cells. Impaired eIF2α phosphorylation enhanced adipocyte differentiation in MEFs, as well as in mice. In contrast, increased eIF2α phosphorylation reduced adipocyte differentiation in 3T3-L1 cells. Forced production of CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), a downstream target of eIF2α phosphorylation, inhibited adipogenesis in 3T3-L1 cells. Mice with deletion of Chop (also known as Ddit3) (Chop (-/-)) gained more fat mass than wild-type mice on HFD. In addition, Chop deletion in genetically obese Lepr (db/db) mice increased body fat mass without altering adipocyte size. In contrast to the eIF2α-CHOP pathway, activation or deletion of Ire1a (also known as Ern1) did not alter adipocyte differentiation in 3T3-L1 cells. CONCLUSIONS/

interpretationThese results demonstrate that eIF2α-CHOP suppresses adipogenesis and limits expansion of fat mass in vivo in mice, rendering this pathway a potential therapeutic target.

Indexed as

Endoplasmic Reticulum Stress3T3-L1 CellsAdipocytesAdipogenesisAnimalsBody CompositionCell DifferentiationEndoribonucleasesEukaryotic Initiation Factor-2FibroblastsGene DeletionMaleMiceMice, Inbred C57BLPhosphorylationProtein Serine-Threonine KinasesEndoribonucleasesErn1 protein, mouseEukaryotic Initiation Factor-2Protein Serine-Threonine KinasesTranscription Factor CHOP

Identifiers

PMID23314846
PMCPMC3606029
OpenAlexW2049110564

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.