Evidence map›Paper›PMID 23497794›Full record

ArticleStem cell research & therapy2013

Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade.

Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D Hinds, Lars Bellner, Dov Goldstein, Stephen J Peterson, Joseph I Shapiro and 1 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

60 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Autophagy: regulating the seesaw of bone-fat balance.Frontiers in cell and developmental biology · 2025
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  4. MicroRNAs as Epigenetic Regulators of Obesity.Advances in experimental medicine and biology · 2024
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  15. Article
  16. Article
  17. Loss of hepatic PPARα promotes inflammation and serum hyperlipidemia in diet-induced obesity.American journal of physiology. Regulatory, integrative and comparative physiology · 2019
    Article
  18. Review
  19. Article
  20. HO-1 overexpression and underexpression: Clinical implications.Archives of biochemistry and biophysics · 2019
    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

11 authors at 5 institutions in 2 countries.

Luca Vanella
Komal Sodhi
Dong Hyun Kim
Nitin Puri
Mani Maheshwari
Terry D Hinds
Lars Bellner
Dov Goldstein
Stephen J Peterson
Joseph I Shapiro
Nader G Abraham
Marshall University · USNew York Medical College · USUniversity of Toledo · USNew Hope Fertility Center · USUniversity of Catania · IT

Funding

Vasoregulatory Function of CYP2E1-Derived EicosanoidsP01HL034300 · NHLBI · NEW YORK MEDICAL COLLEGE · PI SCHWARTZMAN, MICHAL LANIADO · 1985 to 2015
$33.4M
CORAL: Clinical Coordinating CenterU01HL071556 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI COOPER, CHRISTOPHER J · 2004 to 2013
$19.3M
HEME OXYGENASE REGULATION OF EICOSANOID BIOSYNTHESISR01DK056601 · NIDDK · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI ABRAHAM, NADER G. · 2001 to 2013
$4.4M
Receptor Na/K-ATPase Antagonists As Novel Therapeutics For Renal/Cardiac DiseasesR01HL109015 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI SHAPIRO, JOSEPH ISAAC, XIE, ZIJIAN · 2011 to 2014
$2.2M
NHLBI NIH HHS HL-34300NHLBI NIH HHS P01 HL034300NHLBI NIH HHS R01 HL109015NHLBI NIH HHS U01 HL071556NIDDK NIH HHS DK56601
6 · The paper itself

Abstract

introductionHeme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes.

methodsTo verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining.

resultsDuring adipogenesis in vitro, differentiating pre-adipocytes display transient increases in the expression of genes involved in canonical Wnt signaling cascade. Increased levels of HO-1 expression and HO activity resulted in elevated levels of β-catenin, pGSK3β, Wnt10b, Pref-1, and shh along with increased levels of adiponectin (P < 0.05). In addition, induction of HO-1 resulted in a reduction in C/EBPα, PPARγ, Peg-1/Mest, aP2, CD36 expression and lipid accumulation (P < 0.05). Suppression of HO-1 gene by siRNA decreased Wnt10b, pGSK3β and β-catenin expression, and increased lipid accumulation. The canonical Wnt responsive genes, IL-8 and SFRP1, were upregulated by CoPP and their expression was decreased by the concurrent administration of tin mesoporphyrin (SnMP), an inhibitor of HO activity. Furthermore, knockdown of Wnt10b gene expression by using siRNA showed increased lipid accumulation, and this effect was not decreased by concurrent treatment with CoPP. Also our results show that blocking the Wnt 10b antagonist, Dickkopf 1 (Dkk-1), by siRNA decreased lipid accumulation and this effect was further enhanced by concurrent administration of CoPP.

conclusionsThis is the first study to demonstrate that HO-1 acts upstream of canonical Wnt signaling cascade and decreases lipogenesis and adipocyte differentiation suggesting that the HO-1 mediated increase in Wnt10b can modulate the adipocyte phenotype by regulating the transcriptional factors that play a role in adipogenesis. This is evidenced by a decrease in lipid accumulation and inflammatory cytokine levels, increased adiponectin levels and elevation of the expression of genes of the canonical Wnt signaling cascade.

Indexed as

AdipocytesAdipogenesisAdiponectinbeta CateninCD36 AntigensCell DifferentiationCells, CulturedCell SurvivalCytokinesHeme Oxygenase-1HumansIntercellular Signaling Peptides and ProteinsLipidsMesenchymal Stem CellsMetalloporphyrinsProto-Oncogene ProteinsAdiponectinbeta CateninCD36 AntigenscobaltiprotoporphyrinCytokinesDKK1 protein, humanHeme Oxygenase-1Intercellular Signaling Peptides and ProteinsLipidsMetalloporphyrinsProto-Oncogene ProteinsProtoporphyrinsRNA, Small Interferingtin mesoporphyrinWNT10B protein, humanWnt Proteins

Identifiers

PMID23497794
PMCPMC3706794
OpenAlexW2118019707

What OpenQuestion holds

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LicenceCC BY
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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.