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-1α is heavily involved in the shift towards glucose oxidation. p65, which belongs to the NF-κB transcription factor family is another crucial molecule involved in maintaining cardiac homeostasis. There is a substantial amount of evidence suggesting that PGC-1α and NF-κB directly interact, thereby connecting metabolic and inflammatory processes. Dysregulation of either PGC-1α or NF-κB signalling correlates to many diseases including heart disease. In this study, we provide further evidence that the NF-κB family has the ability to repress PGC-1α. We also show that the PGC-1α promoter contains a p65 binding site through which p65 imparts control on the PGC-1α gene. Metabolic homeostasis and inflammation pathways are closely linked and play crucial roles in heart dysfunction.