Evidence mapPaperPMID 42143387Full record

ArticleJournal of translational medicine2026

EDL6D, a bioactive peptide phenocopying SHBG-associated metabolic effects: a new preclinical lead compound for treating the metabolic dysfunction-associated fatty liver disease.

Anna Alvarez-Guaita, Julia Cabrera-Serra, Beatriz Perez-Gonzalez, Maria Teresa Salcedo-Allende, Lidia Fuertes-Rioja, Lorena Ramos-Perez, Cristina Hernandez, Rafael Simó, David M Selva

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Anna Alvarez-GuaitaDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Julia Cabrera-SerraDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Beatriz Perez-GonzalezDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Maria Teresa Salcedo-AllendeHuman Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Lidia Fuertes-RiojaDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Lorena Ramos-PerezDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Cristina HernandezDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Rafael SimóDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain.
David M SelvaDiabetes and Metabolism Research Unit, Vall d' Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Pg Vall d'Hebron 119-129, Barcelona, 08035, Spain. david.martinez.selva@vhir.org.ORCID http://orcid.org/0000-0002-0333-5629

Funding

Agencia Estatal de Investigación CPP2022-009831Agencia Estatal de Investigación PTQ2021-011972Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas N/AEuropean Regional Development Fund N/A
6 · The paper itself

Abstract

backgroundLow plasma sex hormone-binding globulin (SHBG) levels are commonly observed in metabolic dysfunction-associated fatty liver disease (MASLD), a spectrum of disorders ranging from simple hepatocellular steatosis to steatohepatitis, fibrosis, and irreversible cirrhosis. We have previously demonstrated that SHBG overexpression reduces hepatic lipid accumulation by inhibiting lipogenesis both in vitro and in vivo.

methodsIn the present proof-of-concept study, we have developed a bioactive peptide that phenocopies SHBG-associated metabolic effects (EDL6D) and have evaluated its ability to inhibit lipogenesis in vitro using HepG2 cells treated daily with 30 mM fructose. In addition, we assessed the preventive and therapeutic effects of EDL6D in vivo in wild-type mice with MASLD induced by a high-fat diet combined with 30% fructose in drinking water.

resultsTreatment with EDL6D exerted both preventive and therapeutic effects, significantly reducing hepatic fat accumulation and promoting regression of MASLD compared with vehicle-treated mice. Mechanistically, EDL6D downregulated the mRNA expression and protein levels of key lipogenic enzymes, including ATP-citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase, as well as peroxisome proliferator-activated receptor gamma, a central lipogenic transcription factor. Notably, EDL6D prevented the development of mild fibrosis by reducing the expression of collagen type I alpha 1 chain (Col1a1) and transforming growth factor beta 1 (TGF-β1).

conclusionsMASLD remains as an unmet medical need and disease progression to fibrosis represents a major clinical challenge. This study identifies EDL6D as a novel preclinical lead compound that targets both hepatic lipid accumulation and suggests an antifibrotic effect. These findings support the translational potential of bioactive peptides phenocopying SHBG for the treatment and prevention of MASLD.

Indexed as

Fatty LiverMetabolic DiseasesPeptidesAnimalsDiet, High-FatDrug Evaluation, PreclinicalHep G2 CellsHumansLipogenesisLiverMaleMice, Inbred C57BLPeptidesFatty liverFibrosisInflammationLipogenesisPeptideSHBGTriglycerides

Identifiers

PMID42143387
PMCPMC13360854

What Socratic holds

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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.