Peroxisome proliferator-activated receptor α (PPARα) activation advances locomotor activity and feeding daily rhythms in mice

Int J Obes (Lond). 2012 Aug;36(8):1131-4. doi: 10.1038/ijo.2011.215. Epub 2011 Nov 8.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are key mediators of energy homeostasis, and lipid and glucose metabolism that exhibit circadian expression. PPAR activating drugs are used clinically as lipid and glucose-lowering drugs. We evaluated the effect of long-term (11 weeks) PPARα and PPARγ activation using bezafibrate and rosiglitazone, respectively, on metabolism, locomotor activity and feeding rhythms of non-obese mice. We found that bezafibrate, but not rosiglitazone, led to no weight gain and a slight weight loss with reduced epididymal fat pads. Although rosiglitazone had a minor effect on 24-h food intake rhythm, bezafibrate treatment was accompanied by increased amplitude and an advanced acrophase of the 24-h feeding rhythm. Similarly, unlike rosiglitazone, bezafibrate treatment was accompanied by a significantly advanced acrophase of locomotor activity rhythm under constant darkness conditions. As disrupted circadian rhythms lead to obesity, PPARα activation can serve as a clinical target for the modulation of both circadian rhythms and metabolism.

MeSH terms

  • Animals
  • Bezafibrate / pharmacology*
  • Blotting, Western
  • Circadian Rhythm*
  • Feeding Behavior* / drug effects
  • Hypolipidemic Agents / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity* / drug effects
  • PPAR alpha / drug effects
  • PPAR alpha / metabolism*
  • RNA, Messenger
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*
  • Time Factors
  • Transcription Factors / genetics

Substances

  • Hypolipidemic Agents
  • PPAR alpha
  • RNA, Messenger
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Bezafibrate