Temporal control of metabolic amplitude by Nocturnin

The timing of food intake and nutrient utilization is critical to health and regulated in part by the circadian clock. Recently, increased amplitude of circadian oscillations and metabolic output was found to improve health in diabetic and obesity mouse models. Here, we report a novel function for the circadian deadenylase Nocturnin as a regulator of metabolic amplitude across the day/night cycle and in response to nutrient challenge. We show that mice lacking Nocturnin (Noct-/-) display significantly increased amplitudes of mRNA expression of hepatic genes encoding key metabolic enzymes regulating lipid and cholesterol synthesis, both over the daily circadian cycle and in response to fasting and refeeding. Noct-/- mice have increased plasma triglyceride throughout the night and increased amplitude of hepatic cholesterol levels. Therefore, posttranscriptional control by Nocturnin regulates the amplitude of these critical metabolic pathways and loss of this activity results in increased metabolic flux and reduced obesity. Overall design: Total RNA was isolated from liver samples of Wildtype (WT) mice and mice lacking Nocturnin (Noct-/-) and the hepatic transcriptome analyzed by mRNA-seq. WT and Noct-/- mice were on a light:dark LD 12:12 cycle and fed standard chow Ad Libitum.