Abstract
Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and body energy balance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Adipocytes / metabolism*
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Adipocytes / ultrastructure
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Adipose Tissue, Brown / cytology
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Adipose Tissue, Brown / metabolism
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Adipose Tissue, Brown / ultrastructure
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Animals
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Cold Temperature
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Cyclic GMP / metabolism
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DNA, Mitochondrial / metabolism
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DNA-Binding Proteins / metabolism
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Eating
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Energy Metabolism
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Female
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HeLa Cells
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High Mobility Group Proteins
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Humans
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Male
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Mice
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Mice, Knockout
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Mitochondria / metabolism*
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Mitochondria / ultrastructure
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Mitochondrial Proteins*
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Motor Activity
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NF-E2-Related Factor 1
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Nitric Oxide / physiology*
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III
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Nuclear Proteins / metabolism
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Nuclear Respiratory Factors
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Oligonucleotides, Antisense / pharmacology
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Oxadiazoles / pharmacology
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Oxygen Consumption
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Penicillamine / analogs & derivatives*
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Penicillamine / pharmacology
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Quinoxalines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Signal Transduction
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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U937 Cells
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Weight Gain
Substances
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1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
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DNA, Mitochondrial
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DNA-Binding Proteins
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High Mobility Group Proteins
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Mitochondrial Proteins
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NF-E2-Related Factor 1
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Nfe2l1 protein, rat
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Nuclear Proteins
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Nuclear Respiratory Factors
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Oligonucleotides, Antisense
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Oxadiazoles
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Quinoxalines
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RNA, Messenger
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S-nitro-N-acetylpenicillamine
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TFAM protein, human
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Tfam protein, mouse
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Tfam protein, rat
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Trans-Activators
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Transcription Factors
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mitochondrial transcription factor A
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peroxisome-proliferator-activated receptor-gamma coactivator-1
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8-Bromo Cyclic Adenosine Monophosphate
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Nitric Oxide
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NOS3 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III
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Nos3 protein, mouse
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Nos3 protein, rat
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Penicillamine
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Cyclic GMP