The impact of DRP1 on myocardial fibrosis in the obese minipig. (12th February 2020)

• Record Type: Journal Article
• Authors: Chen, Ching‐Yi; Li, Sin‐Jin; Wang, Chia‐Yu; Mersmann, Harry J.; Ding, Shih‐Torng
• Is Part Of: European journal of clinical investigation. Volume 50:Number 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-12
• Subjects: dietary‐induced obesity -- DRP1 -- Lee‐Sung minipigs -- lipotoxicity -- mitochondrial dynamics -- myocardial fibrosis; Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.13204
• Languages: English
• ISSNs: 0014-2972

Abstract

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. Abstract : Mitochondrial dynamics are involved in obesity‐related myocardial fibrosis in Lee‐Sung minipigs. Inhibition of dynamin‐related protein 1 protects the cardiac cells from lipotoxicity. MetS, metabolic syndrome.