Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPARγ activation

We investigated the involvement of basal sympathetic tone in brown adipose tissue (BAT) recruitment and gene expression profile induced by PPARγ activation. Innervated and surgically denervated BAT pads of rats treated or not with rosiglitazone (15 mg•kg•day, 7 days) were evaluated for weight, triacylglycerol and DNA content, mitochondrial mass and gene expression. Rosiglitazone induced BAT recruitment (increased mass, triacylglycerol and DNA content) and mRNA levels of lipolytic (ATGL and CGI58) and lipogenic (LPL, PEPCK, FABP4 and DGAT1) proteins independently of tissue innervation status. Mitochondrial mass and mRNA levels of its regulators PGCα and C/EBPβ were not affected by rosiglitazone, while being significantly reduced by denervation. By contrast, maximal stimulation of UCP1 (thermogenesis), CIDEA (inhibitor of UCP1 activity), MGL (lipolysis), SHP (transcription) and GyK (TAG synthesis) by rosiglitazone depended on the presence of intact BAT innervation. Cold exposure (5°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 PPARγ in vivo depends upon 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 PPARγ-mediated BAT recruitment.