Difference between revisions of "Bonhoure 2015 Genes Dev"
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{{Publication | {{Publication | ||
|title=Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 (2015) Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes Dev 29:934-47. | |title=Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 (2015) Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes Dev 29:934-47. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/25934505 PMID: 25934505] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/25934505 PMID: 25934505] | ||
|authors=Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 | |authors=Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 | ||
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|journal=Genes Dev | |journal=Genes Dev | ||
|abstract=MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences. | |abstract=MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences. | ||
|mipnetlab=CH Lausanne Auwerx J | |||
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{{Labeling | {{Labeling | ||
Revision as of 11:52, 14 July 2015
| Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 (2015) Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes Dev 29:934-47. |
Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 (2015) Genes Dev
Abstract: MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences.
• O2k-Network Lab: CH Lausanne Auwerx J
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Pathology: Obesity, Other
Organism: Mouse Tissue;cell: Liver Preparation: Homogenate
Coupling state: OXPHOS
HRR: Oxygraph-2k
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