Sobotka 2017 MiP2017
Metabolic syndrome is a global health issue and a dominant risk factor for the development of irreversible diseases affecting human metabolism, cardiovascular system and function of a variety of vital organs. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence . NAFLD can predict independent of obesity, the metabolic syndrome and type 2 diabetes . The key metabolic aberrations underlying lipid accumulation in hepatocytes and the progression of NAFLD remain to be elucidated . In this work we investigated the respiration of rat liver mitochondria isolated from rats during the NAFLD progression.
Experiments were performed on male Wistar rats fed with a commercially prepared diet (Altromin) with standard 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 high-resolution respirometry using Oroboros Oxygraph-2k (Innsbruck, Austria) and harmonized respiratory protocols.
During the NAFLD progression we observed increasing micro vesicular steatosis of rat hepatocytes and increased accumulation of triglycerides and cholesterol. These changes were dependent on the duration of HFD feeding. Already after one week of study mitochondrial respiration demonstrated a significant increase in fatty-acid oxidation capacity and ketogenesis. After three weeks we observed an overall increase in mitochondrial respiratory capacity in ET-pathway and OXPHOS state. After six weeks and longer, however, the total mitochondrial capacity for NADH-linked substrates and for succinate was inhibited.
To conclude, the capacity of liver mitochondria to oxidize fatty-acids increase during NAFLD progression. However, the total capacity of electron transfer-pathway of fatty liver mitochondria increased and consequently decreased after 3 and 6 weeks respectively. Our results may suggest an adaptation process followed by the mitochondrial collapse during the development of NAFLD.
Labels: MiParea: Respiration Pathology: Other
Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: OXPHOS, ET Pathway: N, NS HRR: Oxygraph-2k
- Dept Physiology, Fac Medicine Hradec Kralove, Charles Univ, Czech Republic. - [email protected].cz
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