Evidence map›Paper›PMID 38297378›Full record

ArticleGenome medicine2024

Age-dependent genes in adipose stem and precursor cells affect regulation of fat cell differentiation and link aging to obesity via cellular and genetic interactions.

Asha Kar, Marcus Alvarez, Kristina M Garske, Huiling Huang, Seung Hyuk T Lee, Milena Deal, Sankha Subhra Das, Amogha Koka, Zoeb Jamal, Karen L Mohlke and 4 more

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

Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 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

14 authors at 4 institutions in 2 countries.

Asha KarDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.ORCID 0009-0000-1717-1744
Marcus AlvarezDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Kristina M GarskeDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Huiling HuangDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Seung Hyuk T LeeDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Milena DealDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Sankha Subhra DasDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Amogha KokaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Zoeb JamalDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA.
Karen L MohlkeDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Markku LaaksoDepartment of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Sini HeinonenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Kirsi H PietiläinenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Päivi PajukantaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA. ppajukanta@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Helsinki · FIUniversity of Eastern Finland · FIUniversity of North Carolina at Chapel Hill · US

Funding

Genetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2M
Multimodal omics approach to identify health to cardiometabolic disease transitionsR01HL170604 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Paivi Pajukanta · 2023 to 2026
$2.8M
Methods for Genomic Analysis in Heterogeneous TissuesR01HG010505 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HALPERIN, ERAN · 2019 to 2022
$2.6M
Genetics of adipose cell-type expression and cardiometabolic traitsR01DK132775 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MOHLKE, KAREN L., PAJUKANTA, PAIVI · 2022 to 2025
$2.4M
NHGRI NIH HHS R01 HG010505NHLBI NIH HHS R01 HL170604NIDDK NIH HHS R01 DK093757NIDDK NIH HHS R01 DK132775NIH HHS R01DK093757NIH HHS R01DK132775NIH HHS R01HL170604NINR NIH HHS R01HG010505
6 · The paper itself

Abstract

backgroundAge and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner.

methodsWe integrated subcutaneous adipose tissue (SAT) bulk (n=435) and large single-nucleus RNA sequencing (n=105) data with the UK Biobank (UKB) (n=391,701) data to study age-obesity interactions originating from ASPCs by performing cell-type decomposition, differential expression testing, cell-cell communication analyses, and construction of polygenic risk scores for body mass index (BMI).

resultsWe found that the SAT ASPC proportions significantly decrease with age in an obesity-dependent way consistently in two independent cohorts, both showing that the age dependency of ASPC proportions is abolished by obesity. We further identified 76 genes (72 SAT ASPC marker genes and 4 transcription factors regulating ASPC marker genes) that are differentially expressed by age in SAT and functionally enriched for developmental processes and adipocyte differentiation (i.e., adipogenesis). The 76 age-perturbed ASPC genes include multiple negative regulators of adipogenesis, such as RORA, SMAD3, TWIST2, and ZNF521, form tight clusters of longitudinally co-expressed genes during human adipogenesis, and show age-based differences in cellular interactions between ASPCs and adipose cell types. Finally, our genetic data demonstrate that cis-regional variants of these genes interact with age as predictors of BMI in an obesity-dependent way in the large UKB, while no such gene-age interaction on BMI is observed with non-age-dependent ASPC marker genes, thus independently confirming our cellular ASPC results at the biobank level.

conclusionsOverall, we discover that obesity prematurely induces a decrease in ASPC proportions and identify 76 developmentally important ASPC genes that implicate altered negative regulation of fat cell differentiation as a mechanism for aging and directly link aging to obesity via significant cellular and genetic interactions.

Indexed as

Adipose TissueObesityAdipocytesAgingCell DifferentiationHumansTranscription FactorsTranscription FactorsAdipose stem and precursor cells (ASPCs)AgingGene-age interactionsObesityPolygenic risk score (PRS)

Identifiers

PMID38297378
PMCPMC10829214
OpenAlexW4391387855

What OpenQuestion holds

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LicenceCC BY
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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.