Major functions of the hippocampus are to generate, organize and store memory. This is a complex process, which is orchestrated by a group of molecules, called plasticity-related molecules. To control these various plasticity-related molecules at the transcriptional level, we have been endowed with cAMP response element-binding protein (CREB), also known as a master regulator of memory. Interestingly, we have seen that this master regulator is regulated at the transcriptional level in the hippocampus by peroxisome proliferator-activated receptor α (PPARα), a nuclear hormone receptor family transcription factor that is known to control the metabolism of fatty acids in the liver, underlying a possible crosstalk between fat and memory. Although liver PPARα does not directly control hippocampal CREB, this opens up an important possibility to improve hippocampal functions and to be resistant to memory loss by PPARα ligands and maintaining normal levels of PPARα in the hippocampus.