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.
MeSH Terms
3T3 Cells
8-Bromo Cyclic Adenosine Monophosphate/pharmacology
Adipocytes/metabolism,ultrastructure
Adipose Tissue, Brown/cytology,metabolism,ultrastructure
Animals
Cold Temperature
Cyclic GMP/metabolism
DNA, Mitochondrial/metabolism
DNA-Binding Proteins/metabolism
Eating
Energy Metabolism
Female
HeLa Cells
High Mobility Group Proteins
Humans
Male
Mice
Mice, Knockout
Mitochondria/metabolism,ultrastructure
Mitochondrial Proteins
Motor Activity
NF-E2-Related Factor 1
Nitric Oxide/physiology
Nitric Oxide Synthase/genetics,metabolism
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Nuclear Proteins/metabolism
Nuclear Respiratory Factors
Oligonucleotides, Antisense/pharmacology
Oxadiazoles/pharmacology
Oxygen Consumption
Penicillamine/analogs & derivatives,pharmacology
Quinoxalines/pharmacology
RNA, Messenger/genetics,metabolism
Rats
Signal Transduction
Trans-Activators/metabolism
Transcription Factors/metabolism
U937 Cells
Weight Gain
Chemicals
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
DNA, Mitochondrial
DNA-Binding Proteins
High Mobility Group Proteins
Mitochondrial Proteins
NF-E2-Related Factor 1
Nfe2l1 protein, rat
Nuclear Proteins
Nuclear Respiratory Factors
Oligonucleotides, Antisense
Oxadiazoles
Quinoxalines
RNA, Messenger
S-nitro-N-acetylpenicillamine
TFAM protein, human
Tfam protein, mouse
Tfam protein, rat
Trans-Activators
Transcription Factors
mitochondrial transcription factor A
peroxisome-proliferator-activated receptor-gamma coactivator-1
8-Bromo Cyclic Adenosine Monophosphate
Nitric Oxide
NOS3 protein, human
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Nos3 protein, mouse
Nos3 protein, rat
Penicillamine
Cyclic GMP
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Nisoli Enzo
Department of Preclinical Sciences, Center for Study and Research on Obesity, Luigi Sacco Hospital, University of Milan, Milan 20157, Italy.
[email protected]
Clementi Emilio
Paolucci Clara
Cozzi Valeria
Tonello Cristina
Sciorati Clara
Bracale Renata
Valerio Alessandra
Francolini Maura
Moncada Salvador
Carruba Michele O
