Sobotka 2016 Abstract IOC116

Sobotka O, Kucera O, Stankova P, Endlicher R, Nozickova K, Banni A, Cervinkova Z (2016) Mitochondrial respiration in fatty rat liver

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Sobotka O, Kucera O, Stankova P, Endlicher R, Nozickova K, Banni A, Cervinkova Z (2016)

Event: MiPNet21.11 IOC116 Innsbruck AT

Introduction Non-alcoholic fatty liver disease (NAFLD) is a hepatic disorder characterized by increased accumulation of lipids in hepatocytes and by potential advance to an end-stage liver failure (Loomba and Sanyal, 2013). The pathophysiology of NAFLD is associated with insulin resistance, impaired lipid metabolism and increase in reactive oxygen species (ROS) production (Satapati et al., 2015). The vast majority of studies describe some kind of mitochondrial alterations, but facing the critical differences in study designs (type of animal, type and duration of high fat diet, assessment mitochondrial functions) we have to be careful with mitochondrial data interpretation (Kakimoto and Kowaltowski, 2016). In this study we investigate the liver mitochondrial respiration during high-fat and high-cholesterol diet for 1 to 6 weeks. Methods Experiments were performed on male Wistar rats fed with a commercially prepared diet (Altromin) with high cholesterol and high fat content (HFD, 70 % of energy from lard enriched by 1.25 % cholesterol) for 1 and 3 weeks. Histological changes of liver tissue were evaluated by Hematoxylin eosin, Masson’s trichrome and Oil red O staining. Mitochondrial respiration was assessed using OROBOROS Oxygraph 2k with using harmonized reference protocols. Results We observed increased accumulation of lipids and micro vesicular steatosis were present in HFD group after staining by Oil red O and Hematoxylin eosin respectively. We detected higher content of TG and cholesterol in liver homogenates. Mitochondrial respiration demonstrated significant increase in FAO capacity and relative inhibition of succinate stimulated respiration in HFD group. Maximal mitochondrial respiratory capacity was significantly increased after 3 weeks and mitochondria from HFD group exhibited more efficient oxidative phosphorylation. Discussion We described the development of early phase of NAFLD in rats fed by HFD. Already after one week of HFD there was a mild grade of fat accumulation in hepatocytes and liver mitochondria revealed higher capacity for FAO with more pronounced effect after three weeks of HFD. We may thus conclude that mitochondria started an adaptation process to reflect the diet with high fat and high cholesterol content by enhancing their capacity for FAO. Mitochondrial respiration in steatotic rat liver Acknowledgements This work was funded from grants PRVOUK P37/02 and SVV-2016-260287 References KAKIMOTO PA, KOWALTOWSKI AJ: Effects of high fat diets on rodent liver bioenergetics and oxidative imbalance. Redox biology 8: 216-225, 2016. LOOMBA R, SANYAL AJ: The global NAFLD epidemic. Nature reviews Gastroenterology & hepatology 10: 686-690, 2013. SATAPATI S, KUCEJOVA B, DUARTE JA, FLETCHER JA, REYNOLDS L, SUNNY NE, HE T, NAIR LA, LIVINGSTON KA, FU X, MERRITT ME, SHERRY AD, MALLOY CR, SHELTON JM, LAMBERT J, PARKS EJ, CORBIN I, MAGNUSON MA, BROWNING JD, BURGESS SC: Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. The Journal of clinical investigation 125: 4447-4462, 2015.

• Keywords: NAFLD, rat, hepatocytes, fatty acid oxidation

• O2k-Network Lab: CZ Hradec Kralove Cervinkova Z

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Obesity 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase  Regulation: Flux control, Substrate, Fatty acid  Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. 

HRR: Oxygraph-2k