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 γ (PPARγ), PPARγ-coactivator-1α (PGC-1α), 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 °C) for 1, 3, 7, 12, 21 and 45 days were investigated. Particularly, to examine influence of nitric oxide (NO) on IBAT thermogenic-program, cold-exposed animals were treated by l-arginine or Nω-nitro-l-arginine-methyl ester (L-NAME). Related to control (22 ± 1 °C), cold induced time-coordinated UCP1, PPARγ and PGC-1α 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.