Temporal Control of Metabolic Amplitude by Nocturnin

Jeremy J. Stubblefield, Peng Gao, Gokhul Kilaru, Bilal Mukadam, Jeremy Terrien, Carla B. Green

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The timing of food intake and nutrient utilization is critical to health and regulated partly by the circadian clock. Increased amplitude of circadian oscillations and metabolic output has been found to improve health in diabetic and obesity mouse models. Here, we report a 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. Stubblefield et al. find that Nocturnin is a key regulator of metabolic amplitude. Nocturnin expression depends on the circadian clock and nutrient status. In the absence of Nocturnin, mRNAs encoding lipid and cholesterol metabolic enzymes display increased amplitudes of expression, resulting in increased circulating metabolites.

Original languageEnglish (US)
Pages (from-to)1225-1235
Number of pages11
JournalCell Reports
Volume22
Issue number5
DOIs
StatePublished - Jan 30 2018

Keywords

  • amplitude
  • cholesterol
  • circadian
  • deadenylation
  • lipid
  • nocturnin
  • obesity
  • poly(A)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Stubblefield, J. J., Gao, P., Kilaru, G., Mukadam, B., Terrien, J., & Green, C. B. (2018). Temporal Control of Metabolic Amplitude by Nocturnin. Cell Reports, 22(5), 1225-1235. https://doi.org/10.1016/j.celrep.2018.01.011