Pyruvate dehydrogenase complex (PDC) is a key enzyme to control metabolic flux during the fed-fast cycle. Adequate regulation of PDC is very important not only in the rapid selection of fatty acid and glucose metabolism and also in adequate selection of metabolic fate for glycolysis and oxidative phosphorylation. The main mechanism of insulin resistance followed by dietary fat-induced obesity is closely associated with mitochondrial dysfunction and endoplasmic reticulum (ER) stress. In this presentation, we want to show the role of pyruvate dehydrogenases kinase(PDK) involved in dietary fat-induced insulin resistance, used Wild-type (WT) mice and several different models of global pyruvate dehydrogenase kinase(PDK) knockout mice such as PDK2 knockout mice, PDK4 knock mice on fed low fat (LFD) or high fat (HFD) diets.