Focusing on hippocampal gene expression, an in-depth analysis showed an enrichment in pathways involved in energy metabolism and insulin signaling amongst the top 20 upregulated pathways in Bhlhe40 KO hippocampus (e.g. Reactome electron transport chain, Reactome diabetes, Reactome insulin synthesis and secretion, and Reactome glucose regulation of insulin secretion; Fig 5C). This evidence concerns the gene BHLHE40 and diabetes mellitus.