Mitochondrial fusion/fission process involved in the improvement of catalpol on high glucose- induced hepatic mitochondrial dysfunction

• Published in: Acta biochimica et biophysica Sinica Vol. 47; no. 9; pp. 730 - 740
• Main Authors: Xu, Zhimeng, Zhang, Luyong, Li, Xiaojie, Jiang, Zhenzhou, Sun, Lixin, Zhao, Guolin, Zhou, Guohua, Zhang, Heran, Shang, Jing, Wang, Tao
• Format: Journal Article
• Language: English
• Published: China 01.09.2015
• Subjects: Adenosine Triphosphate - metabolism; Animals; ATP含量; Body Weight - drug effects; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - physiopathology; DNA, Mitochondrial - metabolism; Glucose - administration & dosage; Glucose - pharmacology; HepG2细胞; Iridoid Glucosides - pharmacology; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondria, Liver - physiology; Mitochondria, Liver - ultrastructure; Streptozocin; 分裂过程; 功能障碍; 梓醇; 肝线粒体; 肝细胞; 诱导; catalpol; diabetic; liver; mitochondria; fusion/fission
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmv061

Catalpol, an iridoid glycoside, has been shown to exert hypoglycemic effect by rescuing mitochon- drial function, but the detailed mechanism remains unclear yet. In this study, the effect and mechan- ism of catalpol on the hepatic mitochondria under diabetic conditions were further examined. Oral administration of catalpol significantly reduced the blood glucose, triglyceride, and cholesterol levels in high-fat diet- and streptozotocin-induced diabetic mice. Additionally, catalpol attenuated the decrease in liver mitochondrial ATP content resulting from diabetes. Furthermore, the number of mitochondria possessing a long size was increased in catalpol-treated mice. Interestingly, the catal- pol-induced recovery of mitochondrial function was associated with decreased fission protein 1 and dynamin-related protein 1 expression as well as increased mitofusin 1 expression in the liver. In HepG2 cells, catalpol alleviated the decrease of ATP content and mitochondrial membrane potential, and the increase of reactive oxygen species formation induced by high glucose. MitoTracker Green stain shows that the tubular feature of mitochondria was maintained when cells were treated with catalpol. Catalpol also decreased fission protein 1 and dynamin-related protein 1 expression and in- creased mitofusin 1 expression in HepG2 cells. The present results suggest that catalpol can ameli- orate hepatic mitochondrial dysfunction under a diabetic state, and this may be related to its regulation of mitochondrial fusion and fission events.