Hypothyroid state and membrane fatty acid composition influence cardiac mitochondrial pyruvate oxidation.
Pyruvate oxidation was measured in cardiac mitochondria from euthyroid and hypothyroid rats fed diets enriched with either omega-6 or omega-3 fatty acids. Both State 4 and State 3 rates of pyruvate-dependent respiration were markedly reduced in hypothyroid mitochondria, regardless of diet consumed, compared to euthyroid controls. Respiratory control ratios and ADP/O ratios were the same under all treatments. While there was no significant effect of diet on respiration in euthyroid mitochondria, pyruvate oxidation was 28% higher in hypothyroid mitochondria from animals fed the omega-3 diet compared to those fed the omega-6 diet. Depressed respiration in the hypothyroid state was correlated with 18% more phosphatidylcholine in the inner mitochondrial membrane whereas phosphatidylethanolamine was 17% lower and cardiolipin 32% lower compared to controls. The total phospholipid fatty acid composition was not affected by the hypothyroid state. However, enhanced respiration in hypothyroid animals fed the omega-3 diet was associated with a 3-fold increase in monounsaturated fatty acids in the cardiolipin fraction, and a 12-fold increase in omega-3 fatty acids, primarily 22:5(omega-3) and 22:6(omega-3). The data suggest that membrane levels of cardiolipin and its omega-3 fatty acid content modulate pyruvate transport in hypothyroid mitochondria.
Pehowich
D J
DJ
Department of Oral Biology, University of Alberta, Edmonton, Canada.
D000818:Animals; D000090943:Delta-5 Fatty Acid Desaturase; D004041:Dietary Fats / Q000008:administration & dosage; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D007037:Hypothyroidism / Q000378:metabolism*; D007425:Intracellular Membranes / Q000737:chemistry; D050602:Linoleoyl-CoA Desaturase; D008297:Male; D008563:Membrane Lipids / Q000032:analysis*; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010743:Phospholipids / Q000032:analysis; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley
D000090943:Delta-5 Fatty Acid Desaturase; D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D010743:Phospholipids; D011773:Pyruvates; D019289:Pyruvic Acid; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase