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The impact of DRP1 on myocardial fibrosis in the obese minipig
Author(s) -
Chen ChingYi,
Li SinJin,
Wang ChiaYu,
Mersmann Harry J.,
Ding ShihTorng
Publication year - 2020
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13204
Subject(s) - fis1 , downregulation and upregulation , mitochondrial fission , medicine , apoptosis , endocrinology , mfn2 , mitochondrion , oxidative stress , cardiac function curve , fibrosis , myocardial fibrosis , cardiac fibrosis , ventricle , lipotoxicity , mitochondrial fusion , chemistry , biology , insulin resistance , obesity , microbiology and biotechnology , heart failure , biochemistry , mitochondrial dna , gene
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.