Krüppel-like factor 15 (KLF15) has been implicated in energy metabolism in various tissues including muscle, heart, liver, and adipose tissue. The expression of KLF15 is induced by the synergistic action of CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPδ during the differentiation of preadipocytes into adipocytes. The time course of KLF15 expression during this process is similar to that for C/EBPα, and these two proteins appear to promote the differentiation program in a cooperative manner through induction of the peroxisome proliferator-activated receptor γ (PPARγ) gene and other adipocyte-specific genes. A combination of microarray-based chromatin immunoprecipitation and gene expression analyses identified six genes whose promoters bound KLF15 and whose expression was either increased or decreased by forced expression of KLF15 in 3T3-L1 adipocytes. The gene for adrenomedullin, a vasodilatory hormone implicated in the pathogenesis of obesity-induced hypertension and insulin resistance, was one of these genes whose expression appears to be regulated by KLF15. KLF15 may thus also control the function of mature adipocytes through regulation of such genes.