The high-fat diet induces myocardial fibrosis in the metabolically healthy obese minipigs—The role of ER stress and oxidative stress
Resource
Clinical Nutrition
Journal
Clinical
Journal Issue
Nutrition
Pages
-
Date Issued
2016-07
Date
2016-07
Author(s)
Abstract
Background The cellular mechanisms of obesity-induced cardiomyopathy are multiple and not completely elucidated. The objective of this study was to differentiate two obesity-associated cardiomyopathy miniature pig models: one with the metabolic syndrome (MetS), and one with a metabolically healthy obesity (MHO). The cellular responses during the development of obesity-induced cardiomyopathy were investigated. Methods Five-month-old Lee-Sung (MetS) and Lanyu (MHO) minipigs were made obese by feeding a high-fat diet (HFD) for 6 months. Results Obese pigs exhibited a greater heart weight than control pigs. Interstitial and perivascular fibrosis developed in the myocardium of obese pigs. The HFD induced cardiac lipid accumulation and oxidative stress and also decreased the antioxidant defense in MetS pigs. This diet activated oxidative stress without changing cardiac antioxidant defense and lipid content in MHO pigs. The HFD upregulated the expression of Grp94, CHOP, caspase 12, p62, and LC3II, and increased the ratio of LC3II to LC3I in the left ventricle (LV) of MetS pigs. Compared to obese MetS pigs, less Grp94 and elevated CHOP expression was found in the obese MHO heart. The HFD did not change the ratio of LC3II to LC3I and p62 expression in obese MHO pigs. The obese MetS pigs had an extensive and greater inflammatory response in the plasma than the obese MHO pigs, which had a lesser and milder inflammation. Conclusion Oxidative stress and ER stress were involved in the progression of MHO-related cardiomyopathy. Inflammation, autophagy, ER stress, oxidative stress, and lipotoxicity participated in the pathological mechanism of MetS-related cardiomyopathy. ? 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism
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Other Subjects
activating transcription factor 6; antioxidant; caspase 12; chemokine; collagen type 1; endoribonuclease 1alpha; Fas ligand; gamma interferon; gelatinase A; glucose regulated protein 94; granulocyte colony stimulating factor; growth arrest and DNA damage inducible protein 153; interleukin 15; interleukin 17; lipid; lymphotactin; macrophage inflammatory protein 1gamma; microtubule associated protein; microtubule associated protein light chain 3; monocyte chemotactic protein 5; protein kinase; protein kinase RNA like endoplasmic reticulum kinase; ribonuclease; sequestosome 1; somatomedin binding protein; thiobarbituric acid reactive substance; thymus and activation regulated chemokine; transforming growth factor beta1; triacylglycerol; unclassified drug; cytokine; DDIT3 protein, human; glucose-regulated proteins; growth arrest and DNA damage inducible protein 153; heat shock protein 70; membrane protein; microtubule associated protein; triacylglycerol; animal experiment; animal model; animal tissue; Article; autophagy; controlled study; endoplasmic reticulum stress; female; heart left ventricle; heart muscle fibrosis; heart weight; inflammation; lipid diet; lipotoxicity; male; metabolic syndrome X; minipig; nonhuman; obesity; oxidative stress; pathophysiology; protein expression; upregulation; vascular fibrosis; animal; blood; cardiomyopathy; complication; disease model; genetics; lipid diet; metabolism; obesity; pig; Animals; Cardiomyopathies; Cytokines; Diet, High-Fat; Disease Models, Animal; Endoplasmic Reticulum Stress; Female; HSP70 Heat-Shock Proteins; Male; Membrane Proteins; Metabolic Syndrome; Microtubule-Associated Proteins; Obesity; Oxidative Stress; Swine; Swine, Miniature; Transcription Factor CHOP; Triglycerides
Type
journal article
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