Although the AMPK pathway may not be the sole regulator of PXR as it relates to cellular energy status, our present observations, in conjunction with data obtained earlier13, 14, contribute to an improved understanding of drug metabolism and drug clearance in diverse pathophysiologic and nutrient status conditions, including obesity, fasting, and metabolic diseases. Here, NR1I2 is linked to obesity due to melanocortin 4 receptor deficiency.