Bmal1 deletion in mice facilitates adaptation to disrupted light/dark conditions

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Abstract

Recently, by using conventional and tamoxifen-inducible brain and muscle Arnt-like protein 1–knockout (Bmal1-KO) mice, we found that delaying the loss of circadian rhythms to adulthood attenuates the impact on general integrity and survival at least under 12-hour light/12-hour dark conditions. To understand further the contribution of Bmal1 in postnatal life under conditions of circadian disruption, we subjected inducible-KO and their littermate controls (ctrls) to forced desynchrony protocols, including cycles with non–24-hour periods, randomized light/dark cycles, and jet lag, and monitored their locomotor activity using radiotelemetry. Under these conditions, ctrl mice cannot be entrained, as reflected by their maintenance of circadian behavior irrespective of schedules. By contrast, KO mice displayed higher activity levels in the dark phases of most cycles. Under a 3-hour light/3-hour dark regime, ctrls displayed higher activity levels in the dark phases of all cycles, although there were still obvious circadian rhythms, suggesting that an ultradian mechanism is also involved. Insulin sensitivity was markedly reduced by disrupted light schedules, as expected in ctrls, but not in the KO mice. Thus, Bmal1 deletion in adult mice facilitates adaptation to new light/dark schedules and protects from insulin resistance induced by circadian disruption.

Authors

Guangrui Yang, Lihong Chen, Jiayang Zhang, Baoyin Ren, Garret A. FitzGerald