PDK4 and obesity due to melanocortin 4 receptor deficiency: Of note, Hsieh et al. (2010) demonstrated that hyperglycemia in mice with high-fat-diet–induced obesity was associated with alteration of almost all circadian core clock genes, as well as their target genes, namely albumin-D-site-binding protein (Dbp), phosphoenolpyruvate carboxykinase (Pepck), and pyruvate dehydrogenase kinase-4 (Pdk4), which are involved in the circadian transcriptional regulation of several metabolic enzymes, gluconeogenesis, and lipolysis, respectively [19].