Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-gamma activation.
We investigated the involvement of basal sympathetic tone in brown adipose tissue (BAT) recruitment and gene expression profile induced by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation. Innervated and surgically denervated BAT pads of rats treated or not with rosiglitazone (15 mg.kg(-1).day(-1), 7 days) were evaluated for weight, triacylglycerol (TAG) and DNA content, mitochondrial mass, and gene expression. Rosiglitazone induced BAT recruitment (increased mass, TAG and DNA content) and mRNA levels of lipolytic (adipose tissue triglyceride lipase and CGI58) and lipogenic (lipoprotein lipase, phosphoenolpyruvate carboxykinase, fatty acid binding protein 4, and diacylglycerol acyltransferase 1) proteins independently of tissue innervation status. Mitochondrial mass and mRNA levels of its regulators peroxisome proliferator-activated receptor coactivator-alpha and CCAAT/enhancer binding protein-beta were not affected by rosiglitazone, while being significantly reduced by denervation. By contrast, maximal stimulation of uncoupling protein 1 (UCP1) (thermogenesis), cell death-inducing DNA fragmentation factor-45-like effector A (inhibitor of UCP1 activity), monoacylglycerol lipase (lipolysis), small heterodimer partner (transcription), and glycerokinase (TAG synthesis) by rosiglitazone depended on the presence of intact BAT innervation. Cold exposure (5 degrees C, 24 h) significantly increased UCP1 mRNA levels in innervated BAT pads of untreated rats, without affecting the already high BAT UCP1 levels of rosiglitazone-treated animals. A similar pattern of response was found in denervated pads, but with markedly lower UCP1 expression than that in innervated BAT. In conclusion, whereas the mass (hyperplasia and hypertrophy), lipogenic, and lipolytic components of BAT recruitment induced by rosiglitazone occur independently of tissue sympathetic innervation, maximal UCP1 expression induced by PPAR-gamma in vivo depends on the presence of basal BAT adrenergic tone. The residual sympathetic tone found under rosiglitazone treatment is, therefore, involved in the modulation of a subset of major components of PPAR-gamma-mediated BAT recruitment.
Festuccia
William T
WT
Quebec Heart and Lung Institute Research Center, and Department of Medicine, Faculty of Medicine, Laval University, Quebec, Canada.
Blanchard
Pierre-Gilles
PG
Richard
Denis
D
Deshaies
Yves
Y
D002001:Adipose Tissue, Brown / Q000294:innervation* / Q000378:metabolism* / Q000502:physiology; D018663:Adrenergic Agents / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001835:Body Weight; D002460:Cell Line; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D007473:Ion Channels; D008297:Male; D024101:Mitochondrial Proteins; D009638:Norepinephrine / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D022722:Thermogenesis / Q000235:genetics; D045162:Thiazolidinediones; D000071256:Uncoupling Protein 1
D018663:Adrenergic Agents; D051017:Apoptosis Regulatory Proteins; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D011506:Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; C000604371:UCP1 protein, human; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C109664:caspase-activated DNase inhibitor; D000077154:Rosiglitazone; D051048:Diacylglycerol O-Acyltransferase; D009638:Norepinephrine