title: PPARγ activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1α and D2.
abstract: Here, we investigated whether pharmacological PPARγ 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 PPARγ signaling. Sprague-Dawley rats treated or not with the PPARγ ligand rosiglitazone (15 mg·kg(-1)·day(-1), 7 days) were kept at 23°C or exposed to cold (5°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, Vo(2), 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-1α mRNA levels and potentiated the reduction in BAT thyroid hormone receptor (THR) β 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-1α, 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 PPARγ activation impairs short-term cold elicitation of BAT adrenergic and thyroid signaling, which may result in abnormal tissue recruitment and thermogenic activity.
authors.affiliation: Department of Physiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: William T
authors.initials: WT
authors.lastname: Festuccia
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Blanchard
authors.forename: Thiago B
authors.initials: TB
authors.lastname: Oliveira
authors.forename: Juliana
authors.initials: J
authors.lastname: Magdalon
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Paschoal
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D047495:PPAR gamma / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology; D013961:Thyroid Gland / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood; D015854:Up-Regulation / Q000502:physiology*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D013974:Thyroxine; D014157:Transcription Factors; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C501429:Ppargc1a protein, rat