TY - JOUR
T1 - Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity
AU - Coomans, Claudia P.
AU - van den Berg, Sjoerd A. A.
AU - Houben, Thijs
AU - van Klinken, Jan-Bert
AU - van den Berg, Rosa
AU - Pronk, Amanda C. M.
AU - Havekes, Louis M.
AU - Romijn, Johannes A.
AU - van Dijk, Ko Willems
AU - Biermasz, Nienke R.
AU - Meijer, Johanna H.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
U2 - https://doi.org/10.1096/fj.12-210898
DO - https://doi.org/10.1096/fj.12-210898
M3 - Article
C2 - 23303208
SN - 0892-6638
VL - 27
SP - 1721
EP - 1732
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -