Long-term restricted feeding alters circadian expression and reduces the level of inflammatory and disease markers

J Cell Mol Med. 2011 Dec;15(12):2745-59. doi: 10.1111/j.1582-4934.2010.01160.x.


The circadian clock in peripheral tissues can be entrained by restricted feeding (RF), a regimen that restricts the duration of food availability with no calorie restriction (CR). However, it is not known whether RF can delay the occurrence of age-associated changes similar to CR. We measured circadian expression of clock genes, disease marker genes, metabolic factors and inflammatory and allergy markers in mouse serum, liver, jejunum and white adipose tissue (WAT) after long-term RF of 4 months. We found that circadian rhythmicity is more robust and is phase advanced in most of the genes and proteins tested under RF. In addition, average daily levels of some disease and inflammatory markers were reduced under RF, including liver Il-6 mRNA, tumour necrosis factor (TNF)-α and nuclear factor κB (NF-κB) protein; jejunum Arginase, Afp, Gadd45β, Il-1α and Il-1β mRNA, and interleukin (IL)-6 and TNF-α protein and WAT Il-6, Il-1β, Tnfα and Nfκb mRNA. In contrast, the anti-inflammatory cytokine Il-10 mRNA increased in the liver and jejunum. Our results suggest that RF may share some benefits with those of CR. As RF is a less harsh regimen to follow than CR, the data suggest it could be proposed for individuals seeking to improve their health.

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Blotting, Western
  • Body Weight
  • Caloric Restriction*
  • Circadian Rhythm / physiology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Heart / physiology*
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasms / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Thrombosis / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Biomarkers
  • Cytokines
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10