NO modulates the molecular basis of rat interscapular brown adipose tissue thermogenesis

Abstract

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 (PPAR gamma), PPAR gamma-coactivator-1 alpha (PGC-1 alpha), 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 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 N(omega)-nitro-L-arginine-methyl ester (L-NAME). Related to control (22 +/- 1 degrees C), cold induced time-coordinated UCP1, PPAR gamma and PGC-1 alpha 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 mitochondrialremodeling, 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. (C) 2010 Elsevier Inc. All rights reserved.Ministry of Science and Technological Development of the Republic of Serbia [143050]; [COST FA0602 Action