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Involvement of pericardial adipose tissue in cardiac fibrosis of dietary-induced obese minipigs— Role of mitochondrial function

Li, Sin-Jin, Wu, Twin-Way, Chien, Miao-Ju, Mersmann, Harry J., Chen, Ching-Yi
Biochimica et biophysica acta 2019 v.1864 no.7 pp. 957-965
adenosine triphosphate, adipose tissue, adverse effects, apoptosis, cardiomyocytes, energy, fibrosis, high fat diet, interleukin-6, malondialdehyde, miniature swine, mitochondria, oleic acid, pericardium, protein synthesis, saturated fatty acids, swine
Heart is a high energy demand organ and cardiac fat is the main local energy source for heart. Alteration in cardiac fat may affect cardiac energy and contribute to heart dysfunction. We previously observed a link between alteration in pericardial fat (PAT) and local adverse effects on myocardial fibrosis in obese minipigs. This study investigated the role of PAT on cardiac energy and mitochondrial function, and elucidated a potential mechanism for PAT in cardiac fibrosis.Five-month-old Lee-Sung minipigs were made obese by feeding a high-fat diet (HFD) for 6 months. The conditioned medium from PAT of obese minipigs (PAT-CM) was collected and H9C2 cells were treated with it to study mechanisms.HFD caused a cardiac energy deficit and fibrosis in the left ventricle. An elevated content of IL6 and malondialdehyde was found in the PAT of obese pigs. Obese pigs exhibited an increased level of oleic acid and a reduced level of saturated fatty acids in PAT compared to control pigs. HFD did not alter the metabolic characteristics of epicardial fat. PAT-CM caused apoptosis of H9C2 cells and inhibited basal mitochondrial respiration and ATP production. Protein expressions for mitochondrial dynamics- (Mfn2, Opa1, Drp1, and Fis1) and a mitophagy-related protein (Parkin) were suppressed by PAT-CM. PAT-CM enhanced the protein expression of LC3II, and the ratio of LC3II/LC3I.To conclude, PAT was involved in cardiac fibrosis of HFD-fed minipigs. The secretomes of PAT impaired mitochondrial functions and caused cardiomyocyte apoptosis in a paracrine manner.