Abstract
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 and T2D. We discovered that auranofin homed to WAT and improved insulin sensitivity in obese wild-type mice. Auranofin treatment also normalized other obesity-associated abnormalities, including hepatic steatosis and hyperinsulinemia. Surprisingly, the anti-diabetic effects of auranofin required leptin lowering and beta-adrenergic receptors in WAT. These metabolic benefits of leptin reduction were superior to any immune impacts of auranofin in WAT. Our studies reveal important metabolic properties of anti-inflammatory treatments and contribute to the notion that leptin reduction in the periphery can be accomplished to treat obesity and T2D.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.