Obeticholic acid treatment ameliorates the cardiac dysfunction in NASH mice

• DOI: 10.1371/journal.pone.0276717
• Publication Date: 2022-12-09T18:31:11Z
• Authors: Szu-Yu Liu; Chia-Chang Huang; Ying-Ying Yang; Shiang-Fen Huang; Tzung-Yan Lee; Tzu-Hao Li; Ming-Chih Hou; Han-Chieh Lin
• Keywords: Obeticholic acid; Farnesoid X receptor; Cardiac Fibrosis

Background Suppression of cardiac iinflammasome, which can be inhibited by Farnesoid X receptor (FXR) agonist, ameliorate inflammation and fibrosis. Increased inflammasome decrease the abundance regulatory T (Treg) cells exacerbate dysfunction. Interaction between cardiomyocytes Treg is involved in development nonalcoholic steatohepatitis (NASH)-related Aims This study evaluates whether FXR agonist obeticholic acid (OCA) treatment improves NASH-associated Methods The vivo vitro mechanisms effects two weeks OCA on i nflammasome dysregulation-related dysfunction NASH mice (NASH-OCA) at systemic, tissue cellular levels were investigated. Results suppressed serum levels, reduced infiltrated CD3 + cells, increased Treg-represented anti-inflammatory cytokines (IL-10/IL-10R) improved inflammation, fibrosis function [decreased left ventricle (LV) mass fractional shortening (FS)] NASH-OCA mice. percentages OCA-decreased OCA-increased FS positively correlated with percentage IL-10/IL-10R. In from spleen, comparison group, higher intracellular but lower more proliferative/active less apoptotic observed. Incubation H9c2 cardiomyoblasts Treg-NASHcm [supernatant as condition medium (cm)], decreased FXR, downregulated differentiation/contraction marker. Treg-NASHcm-induced hypocontractility attenuated co-incubation OCA, OCA-related abolished siIL-10R pretreatment. Conclusions Chronic activation a potential strategy for activating IL-10/IL-10R signalling, reversing cell dysfunction, improving inflammasome-mediated NASH-related