Dubouchaud 2017 Abstract MITOEAGLE Barcelona
Impact of high-fat diet or PUFAs consumption on the mitochondrial function.
Event: MitoEAGLE Barcelona 2017
Mitochondrial function can be affected by various factors including aging, quantity and quality of the fat in diet, or the level of physical activity. These changes would ultimately be related to development of insulin resistance, liver steatosis and decline in muscle function through exercise intolerance, among other significant consequences. Our general purpose is to study the consequences of high-fat diet or unsaturated fatty acids, such as docosahexaenoic acid (DHA), consumption on the mitochondrial metabolism in various situations including aging, gestational exercise training. We used the model of isolated mitochondria (liver and skeletal muscle) or isolated permeabilized fibers (skeletal muscle). Here we propose to focus on some of our recent results. We showed that DHA supplementation was associated with a higher endurance capacity (+ 56%, p<0.05) compared to control animals. Moreover, permeabilized myofibers from soleus muscle showed higher O2 consumptions (p<0.05) in the DHA group compared to the Control group with glutamate/malate as substrates, both in basal condition (i.e. state 2) and under maximal condition (i.e. state 3, using ADP) along with a higher apparent Km for ADP (p<0.05). These changes were not seen with isolated mitochondria, suggesting that DHA acts on the mitochondrial environment that is of primary importance in the regulation of mitochondrial function. Calcium retention capacity of isolated mitochondria was lower in DHA group compared to the Control group (p<0.05). These suggest that DHA supplementation could be of potential interest for the muscle function through enhancement of the mitochondrial metabolism during early aging. We also have studied the mitochondrial function in offspring from either sedentary or trained (TR) dams before and during gestation. Our results showed that under a control diet, permeabilized isolated muscle fibers of rats from TR dams displayed a lower apparent affinity constant (Km) for pyruvate and palmitoyl Co-A as substrates compared to the rats from CT dams (-46% and -58% respectively, p<0.05). These results suggest that maternal exercise has positive effects on young adult offspring with enhancement in its mitochondrial metabolism when fed with a standard diet. In liver, we found that high-fat diet was associated with State-3 mitochondrial oxidative phosphorylation was inhibition, contrasting with unaffected cytochrome content. Oxidative phosphorylation stoichiometry was unaffected, as were ATPase and adenine nucleotide translocator proteins and mRNAs. Mitochondrial acylcarnitine-related H2O2 production was substantially higher and the mitochondrial quinone pool was smaller and more reduced. Cellular consequences of these mitochondrial alterations were investigated in perifused, freshly isolated hepatocytes. Ketogenesis and fatty acid-dependent respiration were lower, indicating a lower β-oxidation rate. Concomitantly, the cellular redox state was more reduced in the mitochondrial matrix but more oxidized in the cytosol: these opposing changes are in agreement with a significantly higher in situ mitochondrial proton motive force. These results on liver suggest that a high-fat diet results in both a decrease in mitochondrial quinone pool and a profound modification in mitochondrial lipid composition. These changes appear to play a key role in the resulting inhibition of fatty acid oxidation and of mitochondrial oxidative-phosphorylation associated with an increased mitochondrial ROS production.
Labels: MiParea: Respiration, mtDNA;mt-genetics, Exercise physiology;nutrition;life style, Pharmacology;toxicology Pathology: Aging;senescence, Diabetes
Organism: Rat Tissue;cell: Skeletal muscle, Liver Preparation: Permeabilized tissue, Isolated mitochondria
Coupling state: OXPHOS Pathway: F, N
- Univ Grenoble Alpes - INSERM U1055, France