Is There a Defect in Oxidative Metabolism in the Metabolic Syndrome?
A recent study in subjects who were nondiabetic, insulin-resistant and at high risk for diabetes (“prediabetes”), or had type 2 diabetes mellitus, has demonstrated that prediabetic and diabetic muscle is characterized by a decreased expression of genes involved in oxidative phosphorylation, many of which are regulated by nuclear respiratory factor (NRF)-dependent transcription.49 Furthermore, in both prediabetic and diabetic subjects, there is a significant reduction in the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator 1α (PGC-1α), which is an inducible coregulator of nuclear receptors such as NRF involved in the control of mitochondrial biogenesis and functions (Figure 1).50,51 These data indicate that decreased PGC-1α expression may be responsible for the reduced expression of metabolic and mitochondrial genes regulated by NRF and may contribute to the metabolic disturbances characteristic of insulin resistance, diabetes mellitus, and, perhaps, obesi
