Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, China.
J Mol Endocrinol. 2019 Aug;63(2):113-121. doi: 10.1530/JME-18-0242.
The prevalence of obesity is dramatic increased and strongly associated with cardiovascular disease. Adipokines, secreted from adipose tissues, are critical risk factors for the development of cardiomyopathy. Present study aimed to investigate the pathophysiological role of autotaxin in obesity-related cardiomyopathy. In high-fat diet-fed mice, autotaxin was mainly synthesized and secreted from adipocytes. The increased accumulation of cardiac autotaxin was positively associated with cardiac dysfunction in obese mice. Interestingly, specific blockage of adipose tissue autotaxin effectively protected against high-fat diet-induced cardiac structural disorders, left ventricular hypertrophy and dysfunction. Inhibition of autotaxin further improved high-fat diet-induced cardiac fibrosis and mitochondrial dysfunction, including improvement of mitochondrial structure, mass and activities. Our findings demonstrated intervention of adipose tissue biology could influence cardiac modification in obese mice, and adipocyte-derived autotaxin was a potential diagnostic marker and therapeutic target for obesity-related cardiomyopathy.
肥胖的患病率显著增加，并与心血管疾病密切相关。脂肪细胞分泌的脂肪细胞因子是心肌病发展的关键危险因素。本研究旨在探讨自分泌酶在肥胖相关性心肌病中的病理生理作用。在高脂肪饮食喂养的小鼠中，自分泌酶主要由脂肪细胞合成和分泌。心脏自分泌酶的增加与肥胖小鼠的心脏功能障碍呈正相关。有趣的是，脂肪组织自分泌酶的特异性阻断可有效预防高脂肪饮食诱导的心脏结构紊乱、左心室肥厚和功能障碍。自分泌酶的抑制进一步改善了高脂肪饮食诱导的心脏纤维化和线粒体功能障碍，包括改善线粒体结构、质量和活性。我们的研究结果表明，干预脂肪组织生物学可能会影响肥胖小鼠的心脏重塑，脂肪细胞衍生的自分泌酶是肥胖相关性心肌病的潜在诊断标志物和治疗靶点。
