ArticleNature metabolism2022
Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Cross-ancestry genome-wide association studies of liver function biomarkers uncover pleiotropic variants, systemic disease links and therapeutic targets.Genome medicine · 2026Pooled it
- Ternary mTOR-targeted conductive nanofibrous scaffolds with bioactive peptides orchestrate immune-metabolic-fibrotic balance for diabetic bone regeneration.Bioactive materials · 2026Article
- Immunometabolism in Obesity-Associated Type 2 Diabetes: Molecular Mechanisms and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.Aging cell · 2026Article
- Role of hypertrophic adipocytes, collagen VI, and CD38 in adipose tissue fibrosis in obesity.Scientific reports · 2026Article
- C/EBP α is Essential for Gonadal but Not Inguinal White Adipose Tissue Formation in Mice.Obesity (Silver Spring, Md.) · 2026Article
- Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.Protein & cell · 2026Article
- Novel epigenetic marks of insulin resistance trajectories in a longitudinal study of childhood obesity.Cardiovascular diabetology · 2026Article
- The Associations of Anthropometric Indices With Stages and Mortality in Cardiovascular-Kidney-Metabolic Syndrome: Insights From NHANES.Reviews in cardiovascular medicine · 2026Article
- From Human to Mouse and Back Again: Genetic and Genomic Ta(i)les of Islet Dysfunction in Type 2 Diabetes.Annual review of genetics · 2025Review
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.Nature medicine · 2025Article
- A genetic map of human metabolism across the allele frequency spectrum.Nature genetics · 2025Article
- Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Frozen Shoulder as a Metabolic and Immune Disorder: Potential Roles of Leptin Resistance, JAK-STAT Dysregulation, and Fibrosis.Journal of clinical medicine · 2025Review
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- AdipocyteeLife · 2024Article
- Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight.Biomolecules · 2024Review
- Lipid-associated macrophages reshape BAT cell identity in obesity.Cell reports · 2024Article
- Adipocyte-specific FAK deletion promotes pancreatic β-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus.Clinical and translational medicine · 2024Article
Corrections and comments
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Authors and funding
28 authors at 9 institutions in 10 countries.
Funding
Abstract
Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.
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Registered trials
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.