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DOI: 10.1038/s41586-024-08085-6
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Obesity leads to structural and functional maladaptation in adipose tissue, characterized by a reduction in adipocyte progenitor cells (APCs) and a shift toward a pro-inflammatory and fibroinflammatory profile. Treatment with thiazolidinediones (TZDs, PPARγ agonists) like rosiglitazone (Rosi) could efficiently improve insulin sensitivity and reduce inflammation. Despite extensive studies on TZDs' transcriptional effects, the mechanisms through which they regulate translational machinery in adipose tissue under obesity remain poorly understood. In this study, the authors investigated the impaired adaptability of adipose progenitors in obesity, focusing on the role of PPARγ in remodeling translational machinery. They employed single-cell RNA sequencing to examine stromal vascular fraction (SVF) in adipose tissues from obese mice treated with rosiglitazone. They observed transcriptional and translational remodeling including enhanced ribosomal gene expression and selectivity in mRNA translation linked to adipogenesis and lipid metabolism. Polysome profiling revealed significant translational changes despite transcriptional buffering. They demonstrated that heavily translating ribosomes (polysomes) were occupied not only by fat-specific PPARγ targets but also by a distinct selection of transcripts containing specific G-rich motifs in their 5’ untranslated region (5’ UTR) after Rosi treatment. Rosiglitazone-induced remodeling promoted adipose tissue plasticity, improved glucose metabolism, and reduced inflammation in obese mice. These findings highlighted PPARγ's dual role in regulating transcription and translation, offering insights into therapeutic strategies for metabolic diseases.
DOI: 10.1016/j.celrep.2024.114945
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