Peroxisome Proliferator-activated Receptor-γ (PPARγ) modulates hypothalamic regulation

Soumaya Kouidhi , Isabelle Seugnet , Stéphanie Decherf , Hajer Guissouma , Amel Benammar Elgaaied , Barbara Demeneix , Marie-Stéphanie Clerget-Froidevaux

Thyroid hormone receptor (TR) and peroxisome proliferator-activated receptor γ (PPARγ) co-regulate numerous peripheral metabolic responses. To examine potential crosstalk between PPARγ and TRβ in the hypothalamus, thyrotropin-releasing hormone () regulation in the newborn mouse hypothalamus was followed. QPCR showed PPARγ to be expressed in the hypothalamus at this developmental stage. Intra-cerebral injection of PPARγ agonists modified transcription from a construct introduced into the hypothalamus and increased serum thyroxine levels. Furthermore, shRNA-based PPARγ knockdown amplified T-independent transcription and PPARγ overexpression dose-dependently abrogated T-dependent repression. Over-expression of retinoid X receptor-α (RXRα), the common heterodimeric partner of PPARγ and TRβ, rescued PPARγ abrogation of T-dependent repression. Thus, competition for RXR could represent one mechanism underlying this hypothalamic crosstalk between PPARγ and TRβ. These demonstrations of PPARγ effects on hypothalamic transcription consolidate the role of the TRH neuron as a central integrator of energy homeostasis.

Mots clés: gene transfer (iGT); peroxisome proliferator-activated receptor type γ (PPARγ); thyroid hormone receptors (TRs); mouse hypothalamus; thyrotropin-releasing hormone (TRH); transcriptional regulation; gene transfer (iGT).

Soumaya Kouidhi, Isabelle Seugnet, Stéphanie Decherf, Hajer Guissouma, Amel Benammar Elgaaied, et al.. Peroxisome Proliferator-activated Receptor-γ (PPARγ) modulates hypothalamic regulation. Molecular and Cellular Endocrinology, 2010, 317 (1-2), pp.44. ⟨10.1016/j.mce.2009.11.001⟩. ⟨hal-00559591⟩