PPAR gamma activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1 alpha and D2

Autor(es)

Festuccia, William T. ^[1] ; Blanchard, Pierre-Gilles ^[2] ; Oliveira, Thiago B. ^[3] ; Magdalon, Juliana ^[4] ; Paschoal, Vivian A. ^[5] ; Richard, Denis ^[6] ; Deshaies, Yves ^[7]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo. Dept Physiol

^[2] Quebec Heart & Lung Inst. Res Ctr

^[3] Univ Sao Paulo. Dept Physiol

^[4] Univ Sao Paulo. Dept Physiol

^[5] Univ Sao Paulo. Dept Physiol

^[6] Quebec Heart & Lung Inst. Res Ctr

^[7] Quebec Heart & Lung Inst. Res Ctr

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY; v. 303, n. 12, p. R1277-R1285, DEC 2012.
• Citações Web of Science: 12

Resumo

Festuccia WT, Blanchard PG, Oliveira TB, Magdalon J, Paschoal VA, Richard D, Deshaies Y. PPAR gamma activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1 alpha and D2. Am J Physiol Regul Integr Comp Physiol 303: R1277-R1285, 2012. First published October 24, 2012; doi:10.1152/ajpregu.00299.2012.-Here, we investigated whether pharmacological PPAR gamma activation modulates key early events in brown adipose tissue (BAT) recruitment induced by acute cold exposure with the aim of unraveling the interrelationships between sympathetic and PPAR gamma signaling. Sprague-Dawley rats treated or not with the PPAR gamma ligand rosiglitazone (15 mg.kg(-1).day(-1), 7 days) were kept at 23 degrees C or exposed to cold (5 degrees C) for 24 h and evaluated for BAT gene expression, sympathetic activity, thyroid status, and adrenergic signaling. Rosiglitazone did not affect the reduction in body weight gain and the increase in feed efficiency, VO2, and BAT sympathetic activity induced by 24-h cold exposure. Rosiglitazone strongly attenuated the increase in serum total and free T4 and T3 levels and BAT iodothyronine deiodinase type 2 (D2) and PGC-1 alpha mRNA levels and potentiated the reduction in BAT thyroid hormone receptor (THR) beta mRNA levels induced by cold. Administration of T3 to rosiglitazone-treated rats exacerbated the cold-induced increase in energy expenditure but did not restore a proper activation of D2 and PGC-1 alpha, nor further increased uncoupling protein 1 expression. Regarding adrenergic signaling, rosiglitazone did not affect the changes in BAT cAMP content and PKA activity induced by cold. Rosiglitazone alone or in combination with cold increased CREB binding to DNA, but it markedly reduced the expression of one of its major coactivators, CREB binding protein. In conclusion, pharmacological PPAR gamma activation impairs short-term cold elicitation of BAT adrenergic and thyroid signaling, which may result in abnormal tissue recruitment and thermogenic activity. (AU)

• Processo FAPESP: 10/10909-8 - Envolvimento do tecido adiposo no desenvolvimento da obesidade e patologias associadas: investigação dos mecanismos moleculares e busca de novas alternativas terapêuticas
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 09/15354-7 - Envolvimento do tecido adiposo no desenvolvimento da obesidade e patologias associadas: investigação dos mecanismos moleculares e busca de novas alternativas terapêuticas
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores