Evidence map›Paper›PMID 41412283›Full record

ArticleMolecular metabolism2026

Single cell transcriptomics of human weight loss links adipocyte NPY1R to control of lipolysis.

Julius E R Grothen, Jaime M Martinez, Nikos Sidiropoulos, Lucas Massier, Danae Zareifi, Jiawei Zhong, Ida Davidsen, Jette W Platou, Jette Mandelbaum, Pia Rothe and 9 more

Abstract read
In one paragraph

Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

19 authors.

Julius E R GrothenNovo Nordisk A/S, Research & Development, Måløv, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Jaime M MartinezNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Nikos SidiropoulosNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Lucas MassierDepartment of Medicine (H7), Karolinska Institutet, C2-94, Karolinska University Hospital, Huddinge, Sweden; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
Danae ZareifiDepartment of Medicine (H7), Karolinska Institutet, C2-94, Karolinska University Hospital, Huddinge, Sweden.
Jiawei ZhongDepartment of Medicine (H7), Karolinska Institutet, C2-94, Karolinska University Hospital, Huddinge, Sweden.
Ida DavidsenNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Jette W PlatouNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Jette MandelbaumNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Pia RotheNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Henning HvidNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Mads GrønborgNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Christian Toft MadsenNovo Nordisk A/S, Research & Development, Måløv, Denmark.
Jens M BruunSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Danish National Center for Obesity, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Mikael RydénSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Steno Diabetes Center, Copenhagen, Denmark.
Niklas MejhertSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Steno Diabetes Center, Copenhagen, Denmark.
Jørn W HelgeDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Zachary Gerhart-HinesNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. Electronic address: zpg@sund.ku.dk.
Thomas Å PedersenNovo Nordisk A/S, Research & Development, Måløv, Denmark. Electronic address: tqpe@novonordisk.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCombination of increased physical exercise and hypocaloric diet has long been recognized to improve cardiometabolic health and adipose tissue function, including lipid turnover. How such lifestyle interventions mediate benefits at the cellular level remains unknown. Given the critical role of subcutaneous white adipose tissue (scWAT) to systemic metabolic homeostasis, we set out to interrogate how exercise and diet lifestyle intervention impacted scWAT in individuals living with obesity, with a particular focus on lipolytic capacity and cell-specific gene profiling.

methodsSingle nuclei RNA sequencing (snRNAseq) was performed on cryopreserved scWAT biopsies originally collected before and after lifestyle intervention, involving regular exercise and hypocaloric diet in obese individuals. Findings on regulation of lipolysis in adipocytes were followed up with meta-analysis of clinical studies and pharmacological experiments in mature human adipocytes.

resultssnRNAseq analysis revealed intervention-induced changes in all scWAT cell-types. In adipocytes genes linked to protein and organelle turnover, branch chain amino acid catabolism, and lipolytic control were most significantly regulated. We identified a cell autonomous brake on adipocyte lipolysis via the neuropeptide Y receptor 1 (NPY1R). Expression of adipocyte NPY1R was reduced after weight loss and correlated positively with body fat percentage and body mass index. Findings were confirmed in meta-analysis across 23 studies. Finally, we found a negative correlation between NPY1R and beta-adrenergic-induced lipolysis and that NPY dose-dependently attenuated lipolysis and cAMP-signaling in primary human subcutaneous adipocytes.

conclusionsOur work suggests that decreases in adipocyte NPY1R during weight loss boost lipolytic capacity and contribute to improved systemic cardiometabolic health.

Indexed as

AdipocytesLipolysisReceptors, Neuropeptide YTranscriptomeWeight LossAdultExerciseFemaleHumansMaleMiddle AgedObesitySingle-Cell AnalysisSubcutaneous Fatneuropeptide Y-Y1 receptorReceptors, Neuropeptide YClinical cohortHuman adipose tissueLipolysisNeuropeptide Y receptor Y1(NPY1R)snRNAseq (single nuclei RNAseq)Weight loss - Diet and Exercise

Identifiers

PMID41412283
PMCPMC12926987

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.