Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

摘要: Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced activates a comprehensive gene program leads increased mitochondrial oxidative capacity. Once induced, capacity maintained independently rosiglitazone, suggesting additional factors activated. Browning triggers reprogramming PPARγ binding, leading formation “superenhancers” selective for brown-in-white (brite) adipocytes. These highly associated with key brite-selective genes. Based on an association, identified evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), novel transcription is required browning, including increase KLF11 directly induced by appears cooperate feed-forward manner activate maintain program.