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

FASEB J. 2015 Jul;29(7):2905-11. doi: 10.1096/fj.14-267575. Epub 2015 Mar 30.

Abstract

Peroxisome proliferator-activated receptor-α (PPARα) 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 PPARα 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 PPARα 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 PPARα and BMAL1 when switching from the fed to the fasted state, whereas men do not. Interestingly, the PPARα 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 PPARα expression in the fed state might have practical implication in human medicine as PPARα activators like fibrates are used for the therapy of chronic lymphocytic leukemia, microvascular complications in diabetes, and kidney diseases.

Keywords: caloric intake; circadian pacemaker; nuclear receptor.

Publication types

  • Clinical Trial

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Adult
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Eating / genetics
  • Eating / physiology
  • Fasting / metabolism*
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Monocytes / metabolism*
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sex Characteristics
  • Young Adult

Substances

  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • PPAR alpha
  • RNA, Messenger