FGF21 gene therapy as treatment for obesity and insulin resistance

摘要: Abstract Prevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence need novel treatments. Fibroblast growth factor 21 (FGF21) considered a promising therapeutic agent T2D/obesity. Native FGF21 has, however, poor pharmacokinetic properties, making gene therapy an attractive strategy to achieve sustained circulating levels this protein. Here, adeno‐associated viral vectors (AAV) were used genetically engineer liver, adipose tissue, or skeletal muscle secrete FGF21. Treatment animals under long‐term high‐fat diet feeding ob/ob mice resulted marked reductions body weight, tissue hypertrophy inflammation, hepatic steatosis, inflammation fibrosis, insulin resistance > 1 year. This effect was achieved absence side effects despite continuously elevated serum Furthermore, overproduction healthy fed standard prevented increase weight associated with aging. Our study underscores potential treat obesity, resistance, T2D.