Sobotka 2017 MiP2017
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@example.com
- Kucera O and Cervinkova Z (2014) Experimental models of non-alcoholic fatty liver disease in rats. World J Gastroenterol 20:8364-76.
- Yki-Jarvinen H (2010) Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data. Curr Opin Clin Nutr Metab Care 13:709-14.
- Nassir F and Ibdah JA (2014) Role of mitochondria in nonalcoholic fatty liver disease. Int J Mol Sci 15:8713-42.