The impact of DRP1 on myocardial fibrosis in the obese minipig
Journal
European Journal of Clinical Investigation
Journal Volume
50
Journal Issue
3
Date Issued
2020
Author(s)
Abstract
Background: The heart is a highly oxidative tissue, thus mitochondria play a major role in maintaining optimal cardiac function. Our previous study established a dietary-induced obese minipig with cardiac fibrosis. The aim of this study was to elucidate the role of mitochondrial dynamics in cardiac fibrosis of obese minipigs. Design: Four-month-old Lee-Sung minipigs were randomly divided into two groups: a control group (C) and an obese group (O) by feeding a control diet or a high-fat diet (HFD) for 6?months. Exposure of H9c2 cardiomyoblasts to palmitate was used to explore the effects of high-fat on induction of myocardial injury in vitro. Results: The O pigs displayed greater heart weight and cardiac collagen accumulation. Obese pigs exhibited a lower antioxidant capacity, ATP concentration, and higher oxidative stress in the left ventricle (LV). The HFD caused downregulation in protein expression of PGC-1α and OPA1, and upregulation of DRP1, FIS1, and PINK1 in the LV of O compared to C pigs. Furthermore, palmitate induced apoptosis and decreased ATP content in H9c2 cells. Palmitate elevated the protein expression of DRP1 and PINK1 in these cells. Inhibition of DRP1 protein expression by siDRP1 in H9c2 cells resulted in enhanced ATP and decreased palmitate-induced apoptosis. Conclusions: These results suggest that mitochondrial dynamics were linked to the progression of obesity-related cardiac injury. Inhibition of DRP1 after palmitate exposure in H9c2 cells resulted in improved ATP level and decreased apoptosis in vitro suggesting that mitochondrial fission serves a key role in progression of obesity-induced cardiac fibrosis. ? 2020 Stichting European Society for Clinical Investigation Journal Foundation
SDGs
Other Subjects
adenosine triphosphate; collagen; drp1 protein; fis1 protein; mitochondrial protein; opa1 protein; palmitic acid; parkin; peroxisome proliferator activated receptor gamma coactivator 1alpha; pink1 protein; transcription factor FKHR; unclassified drug; voltage dependent anion channel; adenosine triphosphate; dynamin; animal cell; animal experiment; animal model; animal tissue; antioxidant assay; apoptosis; Article; controlled study; disease exacerbation; down regulation; H9c2(2-1) cell line; heart left ventricle; heart muscle fibrosis; heart muscle injury; heart weight; in vitro study; minipig; mitochondrial dynamics; nonhuman; obesity; oxidative stress; priority journal; protein expression; upregulation; animal; breathing; fibrosis; genetics; heart disease; heart mitochondrion; metabolism; obesity; pig; rat; Adenosine Triphosphate; Animals; Dynamins; Fibrosis; Heart Diseases; Mitochondria, Heart; Obesity; Rats; Respiration; Swine; Swine, Miniature
Type
journal article