The Mineralocorticoid Receptor Antagonist Eplerenone Suppresses Interstitial Fibrosis in Subcutaneous Adipose Tissue in Patients With Type 2 Diabetes

Marie Louise Johansen, Jaime Ibarrola, Amaya Fernández-Celis, Morten Schou, Mette Pauli Sonne, Maria Refsgaard Holm, Jon Rasmussen, Flemming Dela, Frederic Jaisser, Jens Faber, Patrick Rossignol, Natalia Lopez-Andres, Caroline Kistorp

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

7 Citationer (Scopus)

Abstract

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association among the MR, fibrosis, and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present substudy, including 30 participants, was prespecified as part of the Mineralocorticoid Receptor Antagonist in Type 2 Diabetes (MIRAD) trial, which randomized patients to either high-dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examination and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen types I and VI, and the profibrotic factor α-smooth muscle actin compared with placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase-associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusion, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind70
Udgave nummer1
Sider (fra-til)196-203
Antal sider8
ISSN0012-1797
DOI
StatusUdgivet - 2021

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