Negative regulation of PGC-1alpha by NF-kappaB

The normal adult heart prefers fatty acids as an energy substrate. In the case of heart failure, the heart switches its preference from fatty acids to glucose, adopting a pattern similar to fetal metabolism. PGC-1alpha is heavily involved in the shift towards glucose oxidation. p65, which belongs to the NF-kappaB transcription factor family is another crucial molecule involved in maintaining cardiac homeostasis. There is a substantial amount of evidence suggesting that PGC-1alpha and NF-kappaB directly interact, thereby connecting metabolic and inflammatory processes. Dysregulation of either PGC-1alpha or NF-kappaB signalling correlates to many diseases including heart disease. In this study, we provide further evidence that the NF-kappaB family has the ability to repress PGC-1alpha. We also show that the PGC-1alpha promoter contains a p65 binding site through which p65 imparts control on the PGC-1alpha gene. Metabolic homeostasis and inflammation pathways are closely linked and play crucial roles in heart dysfunction.