Abstract
SIRT1 is a NAD+-dependent deacetylase implicated in longevity and diverse physiological processes. SIRT1, as a key mediator of beneficial effects of caloric restriction, regulates lipid and glucose metabolism by deacetylating metabolic regulators, as well as histones, in response to nutritional deprivation. Here we discuss how SIRT1 levels are regulated by microRNAs (miRs) which are emerging as important metabolic regulators; the recently identified nuclear receptor FXR/SHP cascade pathway that controls the expression of miR-34a and its target SIRT1; and a FXR/SIRT1 positive feedback regulatory loop, which is deregulated in metabolic disease states. The FXR/miR-34a pathway and other miRs controlling SIRT1 may be useful therapeutic targets for age-related diseases, including metabolic disorders.
MeSH terms
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Animals
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Caloric Restriction
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Cells, Cultured
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Diptera
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Food Deprivation / physiology
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Gene Expression
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Glucose / genetics*
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Glucose / metabolism
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Group III Histone Deacetylases / genetics
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Group III Histone Deacetylases / metabolism
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Humans
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Lipid Metabolism / genetics*
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Longevity / physiology*
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Metabolic Diseases / genetics*
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Metabolic Diseases / metabolism*
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Metabolic Diseases / physiopathology
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Mice
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Mice, Obese
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MicroRNAs / physiology*
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Receptors, Cytoplasmic and Nuclear / physiology
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Signal Transduction
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Sirtuin 1 / physiology*
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Tumor Suppressor Protein p53 / physiology
Substances
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MIRN34 microRNA, human
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MIRN34a microRNA, mouse
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MicroRNAs
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Receptors, Cytoplasmic and Nuclear
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Tumor Suppressor Protein p53
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nuclear receptor subfamily 0, group B, member 2
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Group III Histone Deacetylases
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Sirtuin 1
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Glucose