Peroxisome Proliferator-Activated Receptor-γ-Mediated Positive Energy Balance in the Rat Is Associated with Reduced Sympathetic Drive to Adipose Tissues and Thyroid Status

Peroxisome proliferator-activated receptor-γ (PPARγ) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPARγ activation. Administration of the PPARγ agonist rosiglitazone (15 mg/kg·d) for 7 d to male Sprague Dawley rats increased food intake (10%), feed efficiency (31%), weight gain (45%), spontaneous motor activity (60%), and BAT and WAT mass and reduced whole-body oxygen consumption. Consistent with an anabolic setting, rosiglitazone markedly reduced sympathetic activity to BAT and WAT (>50%) and thyroid status as evidenced by reduced levels of plasma thyroid hormones (T4 and T3) and mRNA levels of BAT and liver T3-generating enzymes iodothyronine type 2 (−40%) and type 1 (−32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of t...