Increased PDK4 mRNA expression is a sensitive marker of upregulated fatty acid oxidation

Publication date: Available online 25 July 2019Source: MitochondrionAuthor(s): Ina Katrine Nitschke Pettersen, Deusdedit Tusubira, Hanan Ashrafi, Sissel Elisabeth Dyrstad, Lena Hansen, Xiao-Zheng Liu, Linn Iren Hodneland Nilsson, Nils Gunnar Løvsletten, Kjetil Berge, Hege Wergedahl, Bodil Bjørndal, Øystein Fluge, Ove Bruland, Arild Christian Rustan, Nils Halberg, Gro Vatne Røsland, Rolf Kristian Berge, Karl Johan TronstadAbstractFatty acid oxidation is a central fueling pathway for mitochondrial ATP production. Regulation occurs through multiple nutrient- and energy-sensitive molecular mechanisms. We explored if upregulated mRNA expression of the mitochondrial enzyme pyruvate dehydrogenase kinase 4 (PDK4) may be used as a surrogate marker of increased mitochondrial fatty acid oxidation, by indicating an overall shift from glucose to fatty acids as the preferred oxidation fuel. The association between fatty acid oxidation and PDK4 expression was studied in different contexts of metabolic adaption. In rats treated with the modified fatty acid tetradecylthioacetic acid (TTA), Pdk4 was upregulated simultaneously with fatty acid oxidation genes in liver and heart, whereas muscle and white adipose tissue remained unaffected. In MDA-MB-231 cells, fatty acid oxidation increased nearly three-fold upon peroxisome proliferator-activated receptor α (PPARα, PPARA) overexpression, and four-fold upon TTA-treatment. PDK4 expression was highly increased under these conditions. Further, ...
Source: Mitochondrion - Category: Biochemistry Source Type: research