Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity

Claudia P. Coomans, Sjoerd A. A. van den Berg, Thijs Houben, Jan-Bert van Klinken, Rosa van den Berg, Amanda C. M. Pronk, Louis M. Havekes, Johannes A. Romijn, Ko Willems van Dijk, Nienke R. Biermasz, Johanna H. Meijer

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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
Original languageEnglish
Pages (from-to)1721-1732
JournalFASEB journal
Issue number4
Publication statusPublished - 2013

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