NO modulates the molecular basis of rat interscapular brown adipose tissue thermogenesis.
Molecular mechanisms underlying interscapular brown adipose tissue (IBAT) thermogenesis were elucidated. Namely, gene and/or protein expression of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARgamma), PPARgamma-coactivator-1alpha (PGC-1alpha), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) - key molecules that regulate thermogenesis-related processes - mitochondriogenesis, angiogenesis and IBAT hyperplasia, in rats subjected to cold (4+/-1 degrees C) for 1, 3, 7, 12, 21 and 45days were investigated. Particularly, to examine influence of nitric oxide (NO) on IBAT thermogenic-program, cold-exposed animals were treated by l-arginine or N(omega)-nitro-l-arginine-methyl ester (L-NAME). Related to control (22+/-1 degrees C), cold induced time-coordinated UCP1, PPARgamma and PGC-1alpha transcriptional activation accompanied by PCNA activation and increased VEGF immunolabeling that correlate with endothelial NO synthase (eNOS) transcriptional activation suggesting NO involvement in these thermogenic-factors activation. Observed molecular changes were translated into increased mitochondrial-remodeling, angiogenesis, and IBAT hyperplasia. l-Arginine augmented and prolonged cold-induced increase of eNOS, inducible NOS and thermogenic-molecules expression, IBAT nerve supply, vascularity, hyperplasia and mitochondrial-remodeling, while L-NAME had an opposite effects. Results show that NO improves thermogenesis-related mitochondriogenesis, angiogenesis and tissue hyperplasia, positively affecting molecular basis of these processes, suggesting that NO is an essential regulator of IBAT thermogenic-program operating, at genes, proteins and tissue structure levels.
Petrović
Vesna
V
University of Belgrade, Institute for Biological Research "Sinisa Stanković", Department of Physiology, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Buzadzić
Biljana
B
Korać
Aleksandra
A
Vasilijević
Ana
A
Janković
Aleksandra
A
Korać
Bato
B
D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D022722:Thermogenesis / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester