Ret finger protein deficiency attenuates adipogenesis in high fat diet-induced obese mice

Ret finger protein (RFP, also known as TRIM27) is a multifunctional protein involved in tumor suppression and transcriptional regulation. While our previous studies revealed RFP's inhibitory role in myogenesis through MyoD regulation, its function in lipid metabolism remained unknown. Here, we investigated the effects of RFP deficiency on adipose metabolism in high-fat diet (HFD)-induced obesity. RFP knockout mice showed significantly reduced weight gain and fat accumulation, along with improved glucose levels and insulin sensitivity compared to wild-type controls. These metabolic improvements were replicated in adipocyte-specific RFP knockout mice. In vitro studies using 3T3-L1 adipocytes demonstrated that RFP regulates adipogenic gene expression through interaction with PPAR-? and interference with its transcriptional activity. Our findings identify RFP as a key regulator balancing skeletal muscle and adipocyte maturation, suggesting that RFP inhibition could be a potential therapeutic target for obesity and metabolic disorders. Overall design: To explore how RFP deficiency affects gene expression, we subjected wild-type and RFP KO mice to a 12-week high-fat diet (HFD) regimen and utilized epididymal white adipose tissue (eWAT) for mRNA sequencing analysis.