Evidence map›Paper›PMID 30737520›Full record

Observational studyDiabetologia2019

Diurnal rhythms in the white adipose tissue transcriptome are disturbed in obese individuals with type 2 diabetes compared with lean control individuals.

Dirk Jan Stenvers, Aldo Jongejan, Sadaf Atiqi, Jeroen P Vreijling, Eelkje J Limonard, Erik Endert, Frank Baas, Perry D Moerland, Eric Fliers, Andries Kalsbeek and 1 more

Open access · hybridAbstract readComparative StudyObservational Study
PubMed Publisher
In one paragraph

Observational study in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.9field-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

39 citing papers in PubMed, 105 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Dirk Jan StenversDepartment of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, room F5-162, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands. d.j.stenvers@amc.uva.nl.ORCID 0000-0002-9519-5140
Aldo JongejanBioinformatics Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Sadaf AtiqiDepartment of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, room F5-162, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands.
Jeroen P VreijlingNeurogenetics Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Eelkje J LimonardDepartment of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, room F5-162, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands.
Erik EndertDepartment of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Frank BaasNeurogenetics Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Perry D MoerlandBioinformatics Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Eric FliersDepartment of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, room F5-162, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands.
Andries KalsbeekDepartment of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, room F5-162, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands.
Peter H BisschopDepartment of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, room F5-162, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands.
Amsterdam University Medical Centers · NLLeiden University Medical Center · NLNetherlands Institute for Neuroscience · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisAnimal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing system for energy metabolism is well established, but little is known about the diurnal regulation of (clock) gene expression in obese individuals with type 2 diabetes. In this study we aimed to identify key disturbances in the diurnal rhythms of the white adipose tissue transcriptome in obese individuals with type 2 diabetes.

methodsIn a case-control design, we included six obese individuals with type 2 diabetes and six healthy, lean control individuals. All participants were provided with three identical meals per day for 3 days at zeitgeber time (ZT, with ZT 0:00 representing the time of lights on) 0:30, 6:00 and 11:30. Four sequential subcutaneous abdominal adipose tissue samples were obtained, on day 2 at ZT 15:30, and on day 3 at ZT 0:15, ZT 5:45 and ZT 11:15. Gene expression was measured using RNA sequencing.

resultsThe core clock genes showed reduced amplitude oscillations in the individuals with type 2 diabetes compared with the healthy control individuals. Moreover, in individuals with type 2 diabetes, only 1.8% (303 genes) of 16,818 expressed genes showed significant diurnal rhythmicity, compared with 8.4% (1421 genes) in healthy control individuals. Enrichment analysis revealed a loss of rhythm in individuals with type 2 diabetes of canonical metabolic pathways involved in the regulation of lipolysis. Enrichment analysis of genes with an altered mesor in individuals with type 2 diabetes showed decreased activity of the translation initiating pathway 'EIF2 signaling'. Individuals with type 2 diabetes showed a reduced diurnal rhythm in postprandial glucose concentrations. CONCLUSIONS/

interpretationDiurnal clock and metabolic gene expression rhythms are decreased in subcutaneous adipose tissue of obese individuals with type 2 diabetes compared with lean control participants. Future investigation is needed to explore potential treatment targets as identified by our study, including clock enhancement and induction of EIF2 signalling. DATA AVAILABILITY: The raw sequencing data and supplementary files for rhythmic expression analysis and Ingenuity Pathway Analysis have been deposited in NCBI Gene Expression Omnibus (GEO series accession number GSE104674).

Indexed as

Circadian RhythmTranscriptomeAdipose Tissue, WhiteAdultAgedARNTL Transcription FactorsBasic Helix-Loop-Helix ProteinsCase-Control StudiesCryptochromesDiabetes Mellitus, Type 2Feeding BehaviorHumansMaleMiddle AgedNerve Tissue ProteinsObesityARNTL Transcription FactorsBasic Helix-Loop-Helix ProteinsBMAL1 protein, humanCRY2 protein, humanCryptochromesNerve Tissue ProteinsNPAS2 protein, humanPER1 protein, humanPER2 protein, humanPER3 protein, humanPeriod Circadian ProteinsCircadian rhythmsClock genesGlucose toleranceLipolysisMetabolic syndromeObesityRNA sequencingTranscriptomicsType 2 diabetesWhite adipose tissue

Identifiers

PMID30737520
OpenAlexW2911866919

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.