The role of peroxisome proliferator-activated receptor-[gamma] coactivator-1[alpha] (PGC-1[alpha]) in increasing mitochondrial content and fatty acid oxidation (FAO) in skeletal muscle has been well described. Often, this increase in mitochondrial content and FAO is observed to associate with increased skeletal muscle and systemic insulin sensitivity. However, to date no studies have documented the effect of elevated PGC-1[alpha] protein expression on hepatocyte mitochondrial function and FAO. Therefore, we examined whether adenoviral PGC-1alpha] protein overexpression would result in increased markers of mitochondrial content and FAO in primary hepatocytes. Additionally, would the increased mitochondrial content and FAO be associated with protection of hepatocyte insulin signaling following chronic exposure to lipids