Sobotka 2016 Abstract IOC116

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Sobotka O, Kucera O, Stankova P, Endlicher R, Nozickova K, Banni A, Cervinkova Z (2016) Mitochondrial respiration in fatty liver. Mitochondr Physiol Network 21.11

Link: Mitochondr Physiol Network 21.11

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

Event: IOC116

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 [1]. The pathophysiology of NAFLD is associated with insulin resistance, impaired lipid metabolism and increase in reactive oxygen species (ROS) production [2]. 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 [3]. In this study we investigate the liver mitochondrial respiration during high-fat and high-cholesterol diet for 1 to 6 weeks.

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, 3 and 6 weeks. Histological changes of liver tissue were evaluated by Hematoxylin eosin, Masson’s trichrome and Oil red O staining. Mitochondrial respiration was assessed by Oroboros Oxygraph-2k using harmonized reference protocols.

We observed increased accumulation of lipids and micro vesicular steatosis was 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 respiratory capacity was significantly increased after 3 weeks and mitochondria from HFD group exhibited more efficient oxidative phosphorylation.

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.

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, ET  Pathway: F, N, S, Gp, CIV, NS, Other combinations, ROX  HRR: Oxygraph-2k 


Affiliations

Dept Physiol, Fac Med Hradec Kralove, Charles Univ in Prague, Czech Republic. - SobotkaO@lfhk.cuni.cz

References and support

  1. Loomba R, Sanyal AJ (2013) The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 10:686-90.
  2. 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 (2015) Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. J Clin Invest 126:1605.
  3. Kakimoto PA, Kowaltowski AJ (2016) Effects of high fat diets on rodent liver bioenergetics and oxidative imbalance. Redox Biol 8:216-25.


This work was funded from grants PRVOUK P37/02 and SVV-2016-260287