Accumulation of auranofin in white adipose tissues lowers leptin levels and exerts anti-diabetic effects

Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and frequently coincides with insulin resistance and type 2 diabetes (T2D). However, pharmacological targeting of WAT inflammation lacks durable therapeutic effects. Through a computational screen, we identified the FDA-approved rheumatoid arthritis drug auranofin is a putative small molecule for obesity treatment. We discovered that allometrically scaled safe auranofin doses homed to WAT and improved insulin sensitivity in obese wild-type mice. To assess the transcriptional changes underlying the beneficial effects of auranofin, we performed RNA-seq analysis on adipose and liver tissue after 4 weeks of treatment with vehicle or auranofin. Comparative gene expression profiling analysis of RNA-seq data for liver, epididymal and inguinal white adipose tissue, and intrascapular brown adipose tissue from C57Bl/6 mice. Mice were ffed 60% HFD diet for 12 weeks before receiving vehicle or auranofin (1 mg/kg BW) 3 times per week for 4 weeks.