Sobotka 2017 Abstract MITOEAGLE Barcelona
The effect of 24 weeks of high-fat and high-cholesterol diet on rat liver mitochondria. Sobotka_Presentation
Event: MitoEAGLE Barcelona 2017
Non-alcoholic fatty liver disease (NAFLD) is characterized as an excess accumulation of fat in the liver by other than alcoholic origin. NAFLD includes a wide range of liver disorders from simple liver steatosis to an end-stage liver failure. Key alterations of mitochondrial physiology associated with hepatocytes fatty changes are described in the literature. In this study we investigated the respiration of rat liver mitochondria isolated from rats fed by high-fat and high-cholesterol diet for 1 to 24 weeks.
Experiments were performed on male Wistar rats fed with a commercially prepared diet (Altromin) with normal fat content (10% of energy) or with high cholesterol and high fat content (HFD, 70% of energy from lard enriched by 1.25% cholesterol) for 1, 3, 6, 12 and 24 weeks. Histological changes of liver tissue were evaluated (Hematoxylin eosin, Masson’s trichrome and Oil red O staining). Mitochondrial respiration was assessed by Oroboros Oxygraph-2k using harmonized reference protocols.
HFD caused increased accumulation of lipids in hepatocytes already after one week of high fat feeding. Although we did not observe any liver fibrosis throughout the duration of this study, we detected microvesicular steatosis by hematoxylin-eosin staining in HFD group in all time periods. In a latter interval (12 weeks) we observed mixed steatosis with zonal distribution. Octanoyl-carnitine and malate initiated mitochondrial OXPHOS respiration was significantly increased after 3-week of high fat feeding and dropped after 6- and 12-week intervals. Relative values of flux control ratio, however, increased already after one week of HFD treatment and dropped after 12 weeks. Flux control factor for octanoyl-carnitin in electron transport system (ET-pathway) state was significantly increased from 1- to 6-week periods. Maximal OXPHOS and ET capacities were greatly enhanced after 3-week HFD feeding and decreased after 6 weeks and longer periods. These findings of mitochondrial respiration in rats fed by HFD may suggest some kind of adaptation of liver mitochondria to the crucial change in diet composition. Overall decline of mitochondrial functions found in latter periods of HFD feeding allows us to suggest possible mitochondrial damage or inhibition of respective parts of respiratory system.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Obesity, Other
Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: OXPHOS, ET Pathway: F, N, S, Gp, ROX HRR: Oxygraph-2k Event: B2
- Dept Physiol, Fac Medicine Hradec Kralove, Charles Univ, Czech Republic. - [email protected]