Evidence map›Paper›PMID 30639037›Full record

ArticleCell stem cell2019

Patient Adipose Stem Cell-Derived Adipocytes Reveal Genetic Variation that Predicts Antidiabetic Drug Response.

Wenxiang Hu, Chunjie Jiang, Dongyin Guan, Pieterjan Dierickx, Rong Zhang, Arden Moscati, Girish N Nadkarni, David J Steger, Ruth J F Loos, Cheng Hu and 3 more

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

Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
3.3field-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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  13. Frontiers in endocrinology · 2022
    Article
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  19. Antidiabetic Properties of Curcumin: Insights on New Mechanisms.Advances in experimental medicine and biology · 2021
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Wenxiang HuInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Chunjie JiangInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Dongyin GuanInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Pieterjan DierickxInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Rong ZhangShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Arden MoscatiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Girish N NadkarniThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
David J StegerInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cheng HuShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai 201499, China.
Weiping JiaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Raymond E SoccioInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Mitchell A LazarInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: lazar@pennmedicine.upenn.edu.
University of Pennsylvania · USShanghai Jiao Tong University · CNIcahn School of Medicine at Mount Sinai · USChild Health and Development Institute · US

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KLAUS H KAESTNER · 1986 to 2026
$48.3M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Nuclear Receptors in Metabolic TissuesR01DK049780 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LAZAR, MITCHELL A. · 1995 to 2025
$10.8M
Transcriptional and epigenomic control of adipose tissue development and functionR01DK098542 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI STEGER, DAVID J. · 2013 to 2017
$1.7M
Translating human PPARy binding regions to gene regulation and metabolic diseaseK08DK094968 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SOCCIO, RAYMOND EDWARD · 2012 to 2016
$775k
Mechanisms of high fat diet-induced circadian hepatic transcription and lipid metabolism reprogrammingF32DK116519 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GUAN, DONGYIN · 2018 to 2020
$148k
NIDDK NIH HHS F32 DK116519NIDDK NIH HHS K08 DK094968NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK020541NIDDK NIH HHS R01 DK049780NIDDK NIH HHS R01 DK098542
6 · The paper itself

Abstract

Thiazolidinedione drugs (TZDs) target the transcriptional activity of peroxisome proliferator activated receptor γ (PPARγ) to reverse insulin resistance in type 2 diabetes, but side effects limit their clinical use. Here, using human adipose stem cell-derived adipocytes, we demonstrate that SNPs were enriched at sites of patient-specific PPARγ binding, which correlated with the individual-specific effects of the TZD rosiglitazone (rosi) on gene expression. Rosi induction of ABCA1, which regulates cholesterol metabolism, was dependent upon SNP rs4743771, which modulated PPARγ binding by influencing the genomic occupancy of its cooperating factor, NFIA. Conversion of rs4743771 from the inactive SNP allele to the active one by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated editing rescued PPARγ binding and rosi induction of ABCA1 expression. Moreover, rs4743771 is a major determinant of undesired serum cholesterol increases in rosi-treated diabetics. These data highlight human genetic variation that impacts PPARγ genomic occupancy and patient responses to antidiabetic drugs, with implications for developing personalized therapies for metabolic disorders.

Indexed as

Genetic VariationAdipocytesAdipose TissueAdultAgedATP Binding Cassette Transporter 1Base SequenceCell LineCholesterolDiabetes Mellitus, Type 2Gene EditingGenetic LociHumansHypoglycemic AgentsMiddle AgedNFI Transcription FactorsABCA1 protein, humanATP Binding Cassette Transporter 1CholesterolHypoglycemic AgentsNFIA protein, humanNFI Transcription FactorsPPAR gammaRosiglitazoneABCA1adipocytesadipose stem cellantidiabetic drugdrug responsegenetic variationPPARγrosiglitazone

Identifiers

PMID30639037
PMCPMC6368460
OpenAlexW2908863468

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.