Obesity and its associated
metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective
therapies. Recently, endocrine
fibroblast growth factors (FGFs) have become attractive targets in the treatment of
metabolic diseases. This review summarizes their most important functions as well as FGF-based
therapies for the treatment of
obesity and
type 2 diabetes (T2D).
RECENT FINDINGS: Recent studies demonstrate that circulating levels of FGF19 are reduced in
obesity. In fact, exogenous FGF19 administration is associated with a reduction in food intake as well as with improvements in glycaemia. In contrast,
FGF21 levels are elevated in subjects with
abdominal obesity,
insulin resistance and T2D, probably representing a compensatory response. Additionally, elevated levels of circulating FGF23 in individuals with
obesity and T2D are reported in most clinical studies. Finally, increased
FGF1 levels in obese patients associated with adipogenesis have been described. FGFs constitute important molecules in the treatment of
metabolic diseases due to their beneficial effects on
glucose and lipid metabolism. Among all members, FGF19 and
FGF21 have demonstrated the ability to improve
glucose,
lipid and energy homeostasis, along with
FGF1, which was recently discovered to have beneficial effects on metabolic homeostasis. Additionally, FGF23 may also play a role in
insulin resistance or energy homeostasis beyond
mineral metabolism control. These results highlight the relevant use of FGFs as potential
biomarkers for the early diagnosis of
metabolic diseases. In this regard, notable progress has been made in the development of FGF-based
therapies and different approaches are being tested in different clinical trials. However, further studies are needed to determine their potential
therapeutic use in the treatment of
obesity and
obesity-related comorbidities.