title: Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity.
abstract: Circadian rhythm disturbances are observed in, e.g., aging and neurodegenerative diseases and are associated with an increased incidence of obesity and diabetes. We subjected male C57Bl/6J mice to constant light [12-h light-light (LL) cycle] to examine the effects of a disturbed circadian rhythm on energy metabolism and insulin sensitivity. In vivo electrophysiological recordings in the central pacemaker of the suprachiasmatic nuclei (SCN) revealed an immediate reduction in rhythm amplitude, stabilizing at 44% of normal amplitude values after 4 d LL. Food intake was increased (+26%) and energy expenditure decreased (-13%), and we observed immediate body weight gain (d 4: +2.4%, d 14: +5.0%). Mixed model analysis revealed that weight gain developed more rapidly in response to LL as compared to high fat. After 4 wk in LL, the circadian pattern in feeding and energy expenditure was completely lost, despite continuing low-amplitude rhythms in the SCN and in behavior, whereas weight gain had stabilized. Hyperinsulinemic-euglycemic clamp analysis revealed complete abolishment of normal circadian variation in insulin sensitivity in LL. In conclusion, a reduction in amplitude of the SCN, to values previously observed in aged mice, is sufficient to induce a complete loss of circadian rhythms in energy metabolism and insulin sensitivity.
authors.affiliation: Leiden University Medical Center, Department of Molecular Cell Biology, Laboratory of Neurophysiology, Bldg. 2, Room T5-32, Einthovenweg 20, PO Box 9600, 2300 RC Leiden, the Netherlands. c.p.coomans@lumc.nl
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Coomans
authors.forename: Sjoerd A A
authors.initials: SA
authors.lastname: van den Berg
authors.forename: Thijs
authors.initials: T
authors.lastname: Houben
authors.forename: Jan-Bert
authors.initials: JB
authors.lastname: van Klinken
authors.forename: Rosa
authors.initials: R
authors.lastname: van den Berg
authors.forename: Amanda C M
authors.initials: AC
authors.lastname: Pronk
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Johanna H
authors.initials: JH
authors.lastname: Meijer
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D059305:Diet, High-Fat; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D001786:Blood Glucose