PDF(Pubmed)
Abstract：
High-fat consumption promotes the development of obesity, which is associated with various chronic illnesses. Mitochondria are the energy factories of eukaryotic cells, maintaining self-stability through a fine-tuned quality-control network. In the present study, we evaluated high-fat diet (HFD)-induced changes in mitochondrial ultrastructure and dynamics protein expression in multiple organs. C57BL/6J male mice were fed HFD or normal diet (ND) for 24 weeks. Compared with ND-fed mice, HFD-fed mice exhibited increased body weight, cardiomyocyte enlargement, pulmonary fibrosis, hepatic steatosis, renal and splenic structural abnormalities. The cellular apoptosis of the heart, liver, and kidney increased. Cellular lipid droplet deposition and mitochondrial deformations were observed. The proteins related to mitochondrial biogenesis (TFAM), fission (DRP1), autophagy (LC3 and LC3-II: LC3-I ratio), and mitophagy (PINK1) presented different changes in different organs. The mitochondrial fusion regulators mitofusin-2 (MFN2) and optic atrophy-1 (OPA1) were consistently downregulated in multiple organs, even the spleen. TOMM20 and ATP5A protein were enhanced in the heart, skeletal muscle, and spleen, and attenuated in the kidney. These results indicated that high-fat feeding caused pathological changes in multiple organs, accompanied by mitochondrial ultrastructural damage, and MFN2 and OPA1 downregulation. The mitochondrial fusion proteins may become promising targets and/or markers for treating metabolic disease.
摘要：
高脂肪消费促进肥胖的发展，这与各种慢性病有关。线粒体是真核细胞的能量工厂,通过微调的质量控制网络保持自我稳定。在本研究中,我们评估了高脂饮食（HFD）诱导的多器官线粒体超微结构和动力学蛋白表达的变化。C57BL/6J雄性小鼠饲喂HFD或正常饮食(ND)24周。与ND喂养的小鼠相比，HFD喂养的小鼠表现出体重增加，心肌细胞增大,肺纤维化，肝脂肪变性,肾脏和脾脏结构异常。心脏的细胞凋亡，肝脏,肾脏增加。观察到细胞脂滴沉积和线粒体变形。与线粒体生物发生（TFAM）相关的蛋白质，裂变（DRP1），自噬（LC3和LC3-II：LC3-I比率），线粒体自噬(PINK1)在不同器官表现出不同的变化。线粒体融合调节因子mitofusin-2（MFN2）和视神经萎缩1（OPA1）在多个器官中始终下调，甚至是脾脏.TOMM20和ATP5A蛋白在心脏中增强，骨骼肌,和脾脏,并在肾脏中减弱。这些结果表明，高脂肪喂养引起多个器官的病理变化，伴有线粒体超微结构损伤，以及MFN2和OPA1下调。线粒体融合蛋白可以成为治疗代谢疾病的有希望的靶标和/或标志物。
