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 language | English (US) |
|---|---|
| Pages (from-to) | 1225-1235 |
| Number of pages | 11 |
| Journal | Cell Reports |
| Volume | 22 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 30 2018 |
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Keywords
- amplitude
- cholesterol
- circadian
- deadenylation
- lipid
- nocturnin
- obesity
- poly(A)
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Temporal Control of Metabolic Amplitude by Nocturnin. / Stubblefield, Jeremy J.; Gao, Peng; Kilaru, Gokhul; Mukadam, Bilal; Terrien, Jeremy; Green, Carla B.
In: Cell Reports, Vol. 22, No. 5, 30.01.2018, p. 1225-1235.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Temporal Control of Metabolic Amplitude by Nocturnin
AU - Stubblefield, Jeremy J.
AU - Gao, Peng
AU - Kilaru, Gokhul
AU - Mukadam, Bilal
AU - Terrien, Jeremy
AU - Green, Carla B.
PY - 2018/1/30
Y1 - 2018/1/30
N2 - 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.
AB - 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.
KW - amplitude
KW - cholesterol
KW - circadian
KW - deadenylation
KW - lipid
KW - nocturnin
KW - obesity
KW - poly(A)
UR - http://www.scopus.com/inward/record.url?scp=85044856582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044856582&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.01.011
DO - 10.1016/j.celrep.2018.01.011
M3 - Article
C2 - 29386110
AN - SCOPUS:85044856582
VL - 22
SP - 1225
EP - 1235
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -