Lindquist 2015 Abstract IOC106
|Alteraas EK, Lindquist C, Berge RK, Bjorndal B (2015) OXPHOS capacity in mouse liver altered by modified fatty acids that inhibit or stimulate beta-oxidation. Mitochondr Physiol Network 20.10.|
Event: IOC106 Schroecken
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries, characterized with high accumulation of triglycerides in the liver. NAFLD is associated with obesity, insulin resistance and dyslipidemia, and has been linked to reduced mitochondrial function. Tetradecylthiopropionic acid (TTP) and Tetradecylthioacetic acid (TTA) are artificial fatty acids, shown to inhibit and increase mitochondrial β-oxidation respectively. They were used to investigate the effect of β-oxidation on mitochondrial respiration as well as important mitochondrial factors. In the present study, C57BL/6JBomTac male mice (n=8-10) were fed a low-fat diet for three weeks supplemented with TTP, TTA, or combined TTP and TTA. As expected, β-oxidation was significantly higher in liver homogenate from TTA-treated mice. TTP treatment decreased hepatic β-oxidation, although not significantly. In accordance with the tendency of inhibited β-oxidation, plasma carnitine and acetylcarnitine levels were lower in TTP-treated mice than in controls, while palmitoylcarnitine levels increased. Concomitantly, liver TAG and cholesterol levels were increased. In contrast, TTA increased plasma carnitine levels, but did not affect liver lipid levels. Interestingly, the combined intervention of TTP + TTA increased β-oxidation and prevented liver TAG and cholesterol accumulation, but despite this an accumulation of plasma palmitoylcarnitine and a decrease in acetylcarnitine was observed. Our results show significantly higher oxidative phosphorylation and maximal capacity of the electron transport system in liver samples from TTA-treated mice. This increase was mainly due to increased complex I activity. TTP did not significantly alter mitochondrial respiration. Strikingly, in mice treated with a combination of TTP and TTA, oxidative phosphorylation was significantly decreased. Our findings suggest that TTA impact the mitochondrial respiration and fatty acid catabolism positively, while TTP did not have any effect on the mitochondrial respiration. Combined, TTA was able to prevent the TTP-induced liver lipid accumulation, but this was linked to a reduced OXPHOS capacity, which could indicate mitochondrial malfunction. More analyses and studies should be done to elaborate this further.
• O2k-Network Lab: NO Bergen Berge RK
Labels: MiParea: Respiration, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style Pathology: Obesity
Organism: Mouse Tissue;cell: Liver Preparation: Homogenate
Coupling state: OXPHOS, ET