Men and women differ in their diurnal expression of monocyte peroxisome proliferator-activated receptor-α in the fed but not in the fasted state

Peroxisome proliferator-activated receptor-alpha (PPAR alpha) plays a pivotal role in regulating metabolic response to fasting and is an inhibitor of inflammatory pathways in immune cells. It represents a therapeutic target for treatment of several diseases, mainly hyperlipidemia. To shed light on PPAR alpha expression changes in response to fasting, young healthy male and female volunteers were fed or fasted for 24 hours. Monocytes were analyzed every 2 hours to compile both profiles of mRNA and protein expression of PPAR alpha and its interactive partner, the circadian pacemaker brain and muscle aryl hydrocarbon receptor nuclear translocator like-1 (BMAL1). We found that women change their diurnal expression profiles of PPAR alpha and BMAL1 when switching from the fed to the fasted state, whereas men do not. Interestingly, the PPAR alpha and BMAL1 profiles of men and women in the fed state are different, whereas the profiles in the fasted state are virtually identical. The finding of diametrically opposite responses of male and female PPAR alpha expression in the fed state might have practical implication in human medicine as PPAR alpha activators like fibrates are used for the therapy of chronic lymphocytic leukemia, microvascular complications in diabetes, and kidney diseases.