Evidence map›Paper›PMID 40000740›Full record

ArticleCommunications medicine2025

LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity.

Nellie Y Loh, Senthil K Vasan, Daniel B Rosoff, Emile Roberts, Andrea D van Dam, Manu Verma, Daniel Phillips, Agata Wesolowska-Andersen, Matt J Neville, Raymond Noordam and 5 more

Abstract read
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In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Reduced Growth and Inflammation in Lrp5Journal of cellular and molecular medicine · 2025
    Article
  3. 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

15 authors.

Nellie Y LohRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-5979-9019
Senthil K VasanRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Daniel B RosoffRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Emile RobertsSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-5729-6290
Andrea D van DamRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Manu VermaRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Daniel PhillipsRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-7242-0598
Agata Wesolowska-AndersenNuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Matt J NevilleRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-6004-5433
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-7801-809X
David W RayRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Jonathan H TobiasMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-7475-3932
Celia L GregsonMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0001-6414-0529
Fredrik KarpeRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-2751-1770
Constantinos ChristodoulidesRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. costas.christodoulides@ocdem.ox.ac.uk.ORCID http://orcid.org/0000-0001-5154-0785

Funding

British Heart Foundation (BHF) FS/16/45/32359Wellcome Trust
6 · The paper itself

Abstract

backgroundWNT signaling plays a key role in postnatal bone formation. Individuals with gain-of-function mutations in the WNT co-receptor LRP5 exhibit increased lower-body fat mass and potentially enhanced glucose metabolism, alongside high bone mass. However, the mechanisms by which LRP5 regulates fat distribution and its effects on systemic metabolism remain unclear. This study aims to explore the role of LRP5 in adipose tissue biology and its impact on metabolism.

methodsMetabolic assessments and imaging were conducted on individuals with gain- and loss-of-function LRP5 mutations, along with age- and BMI-matched controls. Mendelian randomization analyses were used to investigate the relationship between bone, fat distribution, and systemic metabolism. Functional studies and RNA sequencing were performed on abdominal and gluteal adipose cells with LRP5 knockdown.

resultsHere we show that LRP5 promotes lower-body fat distribution and enhances systemic and adipocyte insulin sensitivity through cell-autonomous mechanisms, independent of its bone-related functions. LRP5 supports adipose progenitor cell function by activating WNT/β-catenin signaling and preserving valosin-containing protein (VCP)-mediated proteostasis. LRP5 expression in adipose progenitors declines with age, but gain-of-function LRP5 variants protect against age-related fat loss in the lower body.

conclusionsOur findings underscore the critical role of LRP5 in regulating lower-body fat distribution and insulin sensitivity, independent of its effects on bone. Pharmacological activation of LRP5 in adipose tissue may offer a promising strategy to prevent age-related fat redistribution and metabolic disorders.

Identifiers

PMID40000740
PMCPMC11862225

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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.