Evidence mapPaperPMID 42539331Full record

ArticlebioRxiv : the preprint server for biology2026

Adipocyte Expression of O-Glycoprotein Procollagen C-Endopeptidase Enhancer Protein 2 (PCPE2): Mechanisms Linking Fibrosis and Beiging of White Adipose Tissue.

Mirza A Beg, Hao Xu, Bilal Ahmad, Alexander Rocksvold, Rana K Gupta, Pablo Esteban Morales, Ze Zheng, Wen Dai, Justin Grobe, John J Reho and 12 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Mirza A BegCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.
Hao XuCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.
Bilal AhmadCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.
Alexander RocksvoldCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.
Rana K GuptaDuke Molecular Physiology Institute and Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University School of Medicine, Durham, NC.ORCID 0000-0002-9001-4531
Pablo Esteban MoralesDuke Molecular Physiology Institute and Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University School of Medicine, Durham, NC.
Ze ZhengCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.ORCID 0000-0002-4453-224X
Wen DaiCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.
Justin GrobeCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.ORCID 0000-0001-9737-0873
John J RehoCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.
Yiliang ChenCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.ORCID 0000-0001-9786-8305
Samuel KleinDepartment of Medicine, Washington University, St. Louis, MO.ORCID 0000-0001-7127-1156
Gordon I SmithDepartment of Medicine, Washington University, St. Louis, MO.ORCID 0000-0003-0063-046X
Jong Kyoung KimDepartment of Life Science, Pohang University of Science and Technology, Pohang, South Korea.
Eun Seo ParkDepartment of Life Science, Pohang University of Science and Technology, Pohang, South Korea.
Hahn NahmgoongNational Leader Research Initiatives Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea.ORCID 0000-0003-0518-8682
Jae Bum KimNational Leader Research Initiatives Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea.
Deniz InceDepartment of Chemistry, Yale University, New Haven CT.
Stacy A MalakerDepartment of Chemistry, Yale University, New Haven CT.ORCID 0000-0003-2382-5067
Rachel L MintzDivision of Biological and Biomedical Sciences, Department of Pathology and Immunology, Washington University, St Louis, MO.
Gwendalyn J RandolphDivision of Biological and Biomedical Sciences, Department of Pathology and Immunology, Washington University, St Louis, MO.
Mary G Sorci-ThomasCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI.ORCID 0000-0002-6464-5006

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Procollagen C-endopeptidase enhancer protein 2 (Pcpe2) has been primarily investigated in collagen processing during wound healing and is assumed to function similarly to Pcpe1 in the extracellular matrix (ECM). Our studies suggest that Pcpe2 has unique structural and functional features not shared with Pcpe1. Methods: To study the role of Pcpe2 in adipose tissue remodeling, we created adipose tissue-specific knockout of Pcpe2 (TgAd+Pcpe2KO) and adipose tissue-specific Pcpe2 overexpressing (TgAd+Pcpe2Ox) mice and performed in vivo and ex vivo experiments. Results: We show that TgAd+Pcpe2KO mice are resistant to WD-induced obesity and exhibit reductions in body and fat pad mass. Promethion cage studies showed no significant differences in lean mass or food intake, yet WD-fed TgAd+Pcpe2KO mice exhibited significantly higher energy expenditure than negative Cre littermate controls. WD-fed TgAd+Pcpe2KO mice also showed reduced plasma glucose and lipoprotein lipid concentrations compared to controls. While markers of adipose tissue inflammation were reduced in WD-fed TgAd+Pcpe2KO mice. Examination of mature adipocytes from white adipose tissue showed that WD consumption greatly stimulated Pcpe2 expression, while no change in Pcpe2 expression in the stromal vascular cells was noted. However, in VAT precursor cells (PCs), the CD140b+ population showed a shift from fibroadipogenic precursors towards adipocyte PCs in TgAd+Pcpe2KO mice. This shift in PCs may account for the attenuation of local inflammation and fibrosis in the absence of Pcpe2. Ex vivo differentiation of adipose PCs showed that loss of Pcpe2 enhanced adipocyte differentiation, reducing TGFβ-like signaling via pSmad2/3, and increasing mitochondrial function. Furthermore, unlike Pcpe1, Pcpe2 contains a mucin-like linker domain with nine sites of O-linked glycosylation which may regulate receptor signaling at the plasma membrane. Conclusions: Our results show the ECM O-glycoprotein Pcpe2 is a robust marker of unhealthy adipose tissue expansion in humans and mice and contributes to inflammation and fibrosis associated with WD-induced obesity.

Identifiers

PMID42539331
PMCPMC13419799

What Socratic holds

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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 Socratic graph.