The activation of peroxisome proliferator-activated receptor γ is regulated by Kruppel-like transcription factors 6 & 9 under steatotic conditions

Liver steatosis is characterised by lipid droplet deposition in hepatocytes that can leads to an inflammatory and fibrotic phenotype. Peroxisome proliferator-activated receptors (PPARs) play key roles in energetic homeostasis by regulating lipid metabolism in hepatic tissue. In adipose tissue PPAR gamma regulates the adipocyte differentiation by promoting the expression of lipid-associated genes. Within the liver PPAR gamma is up-regulated under steatotic conditions; however, which transcription factors participate in its expression is not completely understood. Kruppel-like transcription factors (KLFs) regulate various cellular mechanisms, such as cell proliferation and differentiation. KLFs are key components of adipogenesis by regulating the expression of PPAR gamma and other proteins such as the C-terminal enhancer binding protein (C/EBP). Here, we demonstrate that the transcript levels of Klf6, Klf9 and Ppar gamma are increased in response to a steatotic insult in vitro. Chromatin immunoprecipitation (ChIp) experiments showed that klf6 and klf9 are actively recruited to the Ppar gamma promoter region under these conditions. Accordingly, the loss-of-function experiments reduced cytoplasmic triglyceride accumulation. Here, we demonstrated that KLF6 and KLF9 proteins directly regulate PPAR gamma expression under steatotic conditions. (C) 2015 Elsevier Inc. All rights reserved.