Temporal Control of Metabolic Amplitude by Nocturnin
| Autor: | Bilal Mukadam, Jérémy Terrien, Peng Gao, Jeremy J. Stubblefield, Carla B. Green, Gokhul Kilaru |
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| Přispěvatelé: | Mécanismes adaptatifs : des organismes aux communautés (MAOAC), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cholesterol synthesis medicine.medical_specialty [SDV]Life Sciences [q-bio] Circadian clock Regulator Biology Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals RNA Messenger Circadian rhythm lcsh:QH301-705.5 ComputingMilieux_MISCELLANEOUS Mice Knockout 2. Zero hunger Cholesterol Nuclear Proteins Lipid Metabolism medicine.disease Obesity Circadian Rhythm Mice Inbred C57BL Metabolic pathway 030104 developmental biology Endocrinology Liver chemistry lcsh:Biology (General) Flux (metabolism) Transcription Factors |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2018, 22 (5), pp.1225-1235. ⟨10.1016/j.celrep.2018.01.011⟩ Cell Reports, Vol 22, Iss 5, Pp 1225-1235 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. In Brief 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. |
| Databáze: | OpenAIRE |
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