title: Caffeine alters circadian rhythms and expression of disease and metabolic markers.
abstract: The circadian clock regulates many aspects of physiology, energy metabolism, and sleep. Restricted feeding (RF), a regimen that restricts the duration of food availability entrains the circadian clock. Caffeine has been shown to affect both metabolism and sleep. However, its effect on clock gene and clock-controlled gene expression has not been studied. Here, we tested the effect of caffeine on circadian rhythms and the expression of disease and metabolic markers in the serum, liver, and jejunum of mice supplemented with caffeine under ad libitum (AL) feeding or RF for 16 weeks. Caffeine significantly affected circadian oscillation and the daily levels of disease and metabolic markers. Under AL, caffeine reduced the average daily mRNA levels of certain disease and inflammatory markers, such as liver alpha fetoprotein (Afp), C-reactive protein (Crp), jejunum alanine aminotransferase (Alt), growth arrest and DNA damage 45β (Gadd45β), Interleukin 1α (Il-1α), Il-1β mRNA and serum plasminogen activator inhibitor 1 (PAI-1). Under RF, caffeine reduced the average daily levels of Alt, Gadd45β, Il-1α and Il-1β mRNA in the jejunum, but not in the liver. In addition, caffeine supplementation led to decreased expression of catabolic factors under RF. In conclusion, caffeine affects circadian gene expression and metabolism possibly leading to beneficial effects mainly under AL feeding.
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Sherman
authors.forename: Roee
authors.initials: R
authors.lastname: Gutman
authors.forename: Nava
authors.initials: N
authors.lastname: Chapnik
authors.forename: Jenny
authors.initials: J
authors.lastname: Meylan
authors.forename: Johannes
authors.initials: J
authors.lastname: le Coutre
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology*; D031204:Caloric Restriction; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004194:Disease / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D002110:Caffeine