PPARA and heart failure: Previous reports50,51 show that the increased circulating adiponectin levels in patients with heart failure are accompanied by the downregulation of its adiponectin receptor and decreased downstream signaling such as deactivation of the PPAR-α/AMPK pathway and downregulation of several target genes in skeletal muscles, thereby proposing the failure of adiponectin to exert significant beneficial effects (functional adiponectin resistance) in such chronic disease.