title: The high-fat diet induces myocardial fibrosis in the metabolically healthy obese minipigs-The role of ER stress and oxidative stress.
abstract: 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.
  
  
  
  Five-month-old Lee-Sung (MetS) and Lanyu (MHO) minipigs were made obese by feeding a high-fat diet (HFD) for 6 months.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.
authors.forename: Sin-Jin
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Taitung Animal Propagation Station, Livestock Research Institute Council of Agriculture, No. 30, Binlang Vil., Beinan Township, Taitung County, 95444, Taiwan.
authors.forename: Hsien-Pin
authors.initials: HP
authors.lastname: Chu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Mersmann
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.
authors.forename: Shih-Torng
authors.initials: ST
authors.lastname: Ding
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Chu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan. Electronic address: ronichen@ntu.edu.tw.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000209:etiology; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000150:complications; D018384:Oxidative Stress; D013552:Swine; D013556:Swine, Miniature; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D016207:Cytokines; C497249:DDIT3 protein, human; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D014280:Triglycerides; C018551:glucose-regulated proteins; D051742:Transcription Factor CHOP
keywords: Autophagy; Cardiomyopathy; ER stress; Metabolic syndrome; Metabolically healthy obesity; Oxidative stress