Evidence map›Paper›PMID 33228780›Full record

ArticleClinical epigenetics2020

Dynamic changes in chromatin accessibility, altered adipogenic gene expression, and total versus de novo fatty acid synthesis in subcutaneous adipose stem cells of normal-weight polycystic ovary syndrome (PCOS) women during adipogenesis: evidence of cellular programming.

Karen L Leung, Smriti Sanchita, Catherine T Pham, Brett A Davis, Mariam Okhovat, Xiangming Ding, Phillip Dumesic, Tristan R Grogan, Kevin J Williams, Marco Morselli and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  6. Article
  7. On the Intimate Relationship of Adiposity to Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2025
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  17. Artesunate targets cellular metabolism to regulate the Th17/Treg cell balance.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
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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

16 authors at 4 institutions in 1 country.

Karen L LeungDepartment of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Smriti SanchitaDepartment of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Catherine T PhamDepartment of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Brett A DavisDepartment of Medicine, Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland, OR, 97239, USA.
Mariam OkhovatDepartment of Medicine, Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland, OR, 97239, USA.
Xiangming DingTechnology Center for Genomics and Bioinformatics, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Phillip DumesicDana-Farber Cancer Institute, Boston, MA, 02115, USA.
Tristan R GroganDepartment of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Kevin J WilliamsUCLA Lipidomics Lab, Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Marco MorselliDepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Feiyang MaDepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Lucia CarboneDepartment of Medicine, Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland, OR, 97239, USA.
Xinmin LiTechnology Center for Genomics and Bioinformatics, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Daniel A DumesicDepartment of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Gregorio D ChazenbalkDepartment of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. gchazenbalk@mednet.ucla.edu.ORCID 0000-0003-2065-3343
University of California, Los Angeles · USOregon Health & Science University · USDana-Farber Cancer Institute · USOregon National Primate Research Center · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
PROJECT 4: ANDROGEN EXCESS IN ADIPOGENIC DYSFUNCTION IN PCOS WOMENP50HD071836 · NICHD · OREGON HEALTH & SCIENCE UNIVERSITY · PI STOUFFER, RICHARD L · 2014 to 2021
$14.7M
Comparative and functional analysis of conservation and rearrangement of topologically associating domains across mammals.R01HG010333 · NHGRI · OREGON HEALTH & SCIENCE UNIVERSITY · PI CARBONE, LUCIA · 2018 to 2021
$2.8M
NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042NHGRI NIH HHS R01 HG010333NICHD NIH HHS P50 HD071836NIH HHS P51 OD011092
6 · The paper itself

Abstract

backgroundNormal-weight polycystic ovary syndrome (PCOS) women exhibit adipose resistance in vivo accompanied by enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with accelerated lipid accumulation per cell in vitro. The present study examines chromatin accessibility, RNA expression and fatty acid (FA) synthesis during SC abdominal ASC differentiation into adipocytes in vitro of normal-weight PCOS versus age- and body mass index-matched normoandrogenic ovulatory (control) women to study epigenetic/genetic characteristics as well as functional alterations of PCOS and control ASCs during adipogenesis.

resultsSC abdominal ASCs from PCOS women versus controls exhibited dynamic chromatin accessibility during adipogenesis, from significantly less chromatin accessibility at day 0 to greater chromatin accessibility by day 12, with enrichment of binding motifs for transcription factors (TFs) of the AP-1 subfamily at days 0, 3, and 12. In PCOS versus control cells, expression of genes governing adipocyte differentiation (PPARγ, CEBPα, AGPAT2) and function (ADIPOQ, FABP4, LPL, PLIN1, SLC2A4) was increased two-sixfold at days 3, 7, and 12, while that involving Wnt signaling (FZD1, SFRP1, and WNT10B) was decreased. Differential gene expression in PCOS cells at these time points involved triacylglycerol synthesis, lipid oxidation, free fatty acid beta-oxidation, and oxidative phosphorylation of the TCA cycle, with TGFB1 as a significant upstream regulator. There was a broad correspondence between increased chromatin accessibility and increased RNA expression of those 12 genes involved in adipocyte differentiation and function, Wnt signaling, as well as genes involved in the triacylglycerol synthesis functional group at day 12 of adipogenesis. Total content and de novo synthesis of myristic (C14:0), palmitic (C16:0), palmitoleic (C16:1), and oleic (C18:1) acid increased from day 7 to day 12 in all cells, with total content and de novo synthesis of FAs significantly greater in PCOS than controls cells at day 12.

conclusionsIn normal-weight PCOS women, dynamic chromatin remodeling of SC abdominal ASCs during adipogenesis may enhance adipogenic gene expression as a programmed mechanism to promote greater fat storage.

Indexed as

AdipocytesAdipogenesisAdultBody Mass IndexCase-Control StudiesCell DifferentiationChromatinEpigenomicsFatty AcidsFemaleGene ExpressionHumansLipid MetabolismPolycystic Ovary SyndromeRNAStem CellsChromatinFatty AcidsRNATGFB1 protein, humanTransforming Growth Factor beta1AdipogenesisAdipose stem cellsCellular programmingChromatin accessibilityDe novo synthesis of fatty acidsFat storageGene expressionPolycystic ovary syndromeTotal contentTranscriptional factors

Identifiers

PMID33228780
PMCPMC7686698
OpenAlexW3107892275

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.