Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status

Festuccia W. T., Oztezcan S., Laplante M., Berthiaume M., Michel C., Dohgu S., ...More

ENDOCRINOLOGY, vol.149, no.5, pp.2121-2130, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 149 Issue: 5
  • Publication Date: 2008
  • Doi Number: 10.1210/en.2007-1553
  • Journal Name: ENDOCRINOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2121-2130
  • Istanbul University Affiliated: Yes


Peroxisome proliferator-activated receptor-gamma (PPAR gamma) 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 PPAR gamma activation. Administration of the PPAR gamma agonist rosiglitazone (15 mg/kg center dot 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 (T-4 and T-3) and mRNA levels of BAT and liver T-3-generating enzymes iodothyronine type 2 (-40%) and type 1 (-32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of the thyroid hormone receptor (THR) isoforms alpha 1 (-34%) and beta (-66%) in BAT and isoforms alpha 1 (-20%) and alpha 2 (-47%) in retroperitoneal WAT. These metabolic effects were associated with a reduction in mRNAlevels of the pro-energy expenditure peptides CRH and CART in specific hypothalamic nuclei. A direct central action of rosiglitazone is, however, unlikely based on its low brain uptake and lack of metabolic effects of intracerebroventricular administration. In conclusion, a reduction in BAT sympathetic activity and thyroid status appears to, at least partly, explain the PPAR gamma-induced reduction in energy expenditure and the fact that up-regulation of thermogenic gene expression does not translate into functional stimulation of whole-body thermogenesis in vivo.