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 the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity. Native FGF21 has, however, poor pharmacokinetic properties, making gene therapy an attractive strategy to achieve sustained circulating levels of this protein. Here, adeno-associated viral vectors (AAV) were used to genetically engineer liver, adipose tissue, or skeletal muscle to secrete FGF21. Treatment of animals under long-term high-fat diet feeding or of ob/ob mice resulted in marked reductions in body weight, adipose tissue hypertrophy and inflammation, hepatic steatosis, inflammation and fibrosis, and insulin resistance for > 1 year. This therapeutic effect was achieved in the absence of side effects despite continuously elevated serum FGF21. Furthermore, FGF21 overproduction in healthy animals fed a standard diet prevented the increase in weight and insulin resistance associated with aging. Our study underscores the potential of FGF21 gene therapy to treat obesity, insulin resistance, and T2D.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Jimenez V,Jambrina C,Casana E,Sacristan V,Muñoz S,Darriba S,Rodó J,Mallol C,Garcia M,León X,Marcó S,Ribera A,Elias I,Casellas A,Grass I,Elias G,Ferré T,Motas S,Franckhauser S,Mulero F,Navarro M,Haurigot V,Rubedoi
10.15252/emmm.201708791subject
Has Abstractpub_date
2018-08-01 00:00:00issue
8eissn
1757-4676issn
1757-4684pii
emmm.201708791journal_volume
10pub_type
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