The fibroblast growth factor (FGF) 11 subfamily consists of FGF11, FGF12, FGF13, and FGF14. The FGF11 subfamily is independent of the other subfamilies, with its most notable characteristic being that the proteins are intracellular, non-secreted. Consequently, the FGF11 subfamily members function independently of the fibroblast growth factor receptor (FGFR). Furthermore, two splice isoforms of FGF13 have been identified: FGF13A, which contains a nuclear localization signal (NLS), and FGF13B, which lacks the NLS and is cytoplasmic.
(Data source: Zhang X, et al. Sci China Life Sci. 2012)
(Data source: AlphaFold)
FGF11 consists of 225 amino acids, has no signal peptide, and its main functional domain is a full-length segment, which includes a disordered structural segment.
(Data source: Uniprot)
Compared to other members, the activity, function, and molecular mechanisms of FGF11 have not been well studied. Currently, apart from some studies focusing on FGF11's role in regulating cancer progression, there are few reports on FGF11. Below, we will focus on the research progress of FGF11 in adipocyte regulation and obesity.
During 3T3-L1 adipocyte differentiation, FGF11 expression decreases during the mitotic expansion stage and increases during the terminal differentiation stage.
(Data source: ee KW, et al. FEBS Open Bio. 2019)
Further knockdown of FGF11 revealed that it reduced the expression of peroxisome proliferator-activated receptor γ (PPARγ), a major regulator of adipogenesis, leading to the inhibition of adipocyte differentiation, indicating that FGF11 is a potential mediator of adipogenesis.
(Data source: ee KW, et al. FEBS Open Bio. 2019)
Subsequent exploration of the role and function of FGF11 in systemic metabolic regulation: Injecting FGF11 shRNA lentivirus into the arcuate nucleus of the hypothalamus of mice (the hypothalamus is one of the most important brain areas that controls metabolism (including food intake and glucose and energy metabolism), and the two major neuronal groups located in the arcuate nucleus of the hypothalamus play an important role in regulating metabolism) can reduce weight gain and fat mass, increase brown adipose tissue thermogenesis, and improve glucose and insulin intolerance under high-fat diet conditions, further indicating that FGF11 is a potential target for the treatment of obesity-related diseases.
(Data source: Kim EK, et al. Mol Brain. 2022)
