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FGF21 gene therapy as treatment for obesity and insulin resistance

Veronica Jimenez1,2,3, Claudia Jambrina1,2,3, Estefania Casana1,2,3

  • 1Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain.

EMBO Molecular Medicine
|July 11, 2018
PubMed

Insights

Gene therapy using fibroblast growth factor 21 (FGF21) offers a potential long-term treatment for obesity and type 2 diabetes (T2D). This approach successfully reduced body weight and improved metabolic health in animal models.

Area of Science:

  • Metabolic diseases
  • Gene therapy
  • Endocrinology

Background:

  • Rising global prevalence of type 2 diabetes (T2D) and obesity necessitates novel therapeutic strategies.
  • Existing treatments for T2D and obesity are not universally effective due to population heterogeneity.
  • Fibroblast growth factor 21 (FGF21) shows therapeutic promise, but native forms have poor pharmacokinetics.

Purpose of the Study:

  • To evaluate the efficacy of FGF21 gene therapy for treating T2D and obesity.
  • To assess the long-term metabolic benefits and safety of sustained FGF21 production.
  • To explore FGF21's potential in preventing age-related metabolic decline.

Main Methods:

  • Adeno-associated viral vectors (AAV) were employed for FGF21 gene delivery to liver, adipose, or skeletal muscle.
  • Animal models, including those on high-fat diets and ob/ob mice, were utilized.
  • Metabolic parameters, body weight, and tissue health were monitored over extended periods.

Main Results:

  • Sustained FGF21 secretion via gene therapy led to significant reductions in body weight and adipose tissue hypertrophy/inflammation.
  • Improvements were observed in hepatic steatosis, inflammation, fibrosis, and insulin resistance lasting over a year.
  • FGF21 gene therapy prevented weight gain and insulin resistance in healthy animals during aging, with no observed side effects.

Conclusions:

  • FGF21 gene therapy represents a promising strategy for durable treatment of obesity and T2D.
  • This approach effectively addresses multiple facets of metabolic dysfunction.
  • Gene therapy offers a viable alternative to overcome the pharmacokinetic limitations of native FGF21.
Keywords:
AAV gene therapyFGF21insulin resistanceobesitytype 2 diabetes

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