The cytochrome P450 enzyme Cyp17a1 catalyzes intermediate reactions in the synthesis of all steroid hormones. Metabolic regulation by the liver is under the control of members of the nuclear receptor class of transcription factors, with farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARα) playing important roles. Milona et al. discovered that Cyp17a1 is repressed by FXR action in the liver in the fed state. During starvation, Cyp17a1 is de-repressed and produces a hormone ligand for PPARα. The authors show that hepatic Cyp17a1-dependent PPARα-activity is essential for the maintenance of fasting glucose and ketone levels. This is an important new link between extra-gonadal steroidogenic pathways and a nutrient responsive nuclear receptor network.