Altered Body Weight Regulation in CK1ϵ Null and tau Mutant Mice on Regular Chow and High Fat Diets

Abstract

Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ϵ) is a canonical circadian clock gene. Null and tau mutations in CK1ϵ show distinct effects on circadian period. To investigate the role of CK1ϵ in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1 ϵ - / - and CK1 ϵ t a u / t a u mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1 ϵ t a u / t a u mice on a 24 hr LD cycle, a separate set of CK1 ϵ t a u / t a u mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1 ϵ - / - and CK1 ϵ t a u / t a u mutants on a 24 hr LD cycle and CK1 ϵ t a u / t a u mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1 ϵ t a u / t a u mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ϵ involved in the integration of circadian biology and metabolic physiology.