Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation and is closely linked to the development of obesity. Despite great progress in elucidating the transcriptional network of PPARγ, epigenetic regulation of this pathway by histone modification remains elusive. Here, we found that CDK2-associated cullin 1 (CACUL1), identified as a novel SIRT1 interacting protein, directly bound to PPARγ through the co-repressor nuclear receptor (CoRNR) box 2 and repressed the transcriptional activity and adipogenic potential of PPARγ. Upon CACUL1 depletion, less SIRT1 and more LSD1 were recruited to the PPARγ-responsive gene promoter, leading to increased histone H3K9 acetylation, decreased H3K9 methylation, and PPARγ activation during adipogenesis in 3T3-L1 cells. These findings were reversed upon fasting or resveratrol treatment. Further, gene expression profiling using RNA sequencing supported the repressive role of CACUL1 in PPARγ activation and fat accumulation. Finally, we confirmed CACUL1 function in human adipose-derived stem cells. Overall, our data suggest that CACUL1 tightly regulates PPARγ signaling through the mutual opposition between SIRT1 and LSD1, providing insight into its potential use for anti-obesity treatment.

Early diagnosis and treatment of rheumatoid arthritis (RA) are of critical importance to halt the progression of the disease. Optimal use of advanced imaging techniques or biomarkers may facilitate early diagnosis of RA. Even though many disease-modifying anti-rheumatic drugs (DMARDs) are available for RA treatment, biological DMARDs (bDMARDs) offer expanding therapeutic options and good outcomes in patients with RA who do not have a sufficient response to conventional synthetic DMARDs. However, high costs of bDMARDs have limited patient access to optimised disease management and increased the cost burden for healthcare systems. The advent of biosimilars led to significant cost savings driven by price competition among the reference products, which could be beneficial for healthcare systems. Healthcare provider (HCP)–patient communication and informed shared decision-making are crucial to prevent the occurrence of a nocebo effect, which results from negative perceptions that patients may have and could lead to less effective outcomes. Research has demonstrated that effective communication between HCPs and patients utilising positive framing can improve acceptance by patients to be initiated on or switched to a biosimilar and can help to integrate biosimilars into routine clinical practice to maximise benefits for patients with RA.