Recent evidence has documented a potentially important new role for visfatin in the context of metabolic disease, showing that visfatin upregulates ECM proteins including osteopontin (Opn), collagen type VI, MMP-2, and MMP-9 in 3T3-L1 pre-adipocytes, and induces Opn gene expression via PI3K, JNK, MAPK/ERK, and NOTCH1 [15]. This evidence concerns the gene SPP1 and metabolic disease.