Roles of FGFs as Adipokines in Adipose Tissue Development, Remodeling, and Metabolism

Abstract

White and brown adipose tissues (BATs), which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among 22 FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and BATs. FGF1 is a critical transducer in white adipose tissue (WAT) remodeling. The peroxisome proliferator-activated receptor γ–FGF1 axis is critical for energy homeostasis. FGF10 is essential for embryonic white adipocyte development. FGF21 activates BAT in response to cold exposure. FGF21 also stimulates the accumulation of brown-like cells in WAT during cold exposure and is an upstream effector of adiponectin, which controls systemic energy metabolism. These findings provide new insights into the roles of FGF signaling in white and BATs and potential therapeutic strategies for metabolic disorders.

Evidence for the involvement of Fibroblast Growth Factor 10 in lipofibroblast formation during embryonic lung development

“…The present findings provide new evidence that LIF formation depends on Fgf10 signaling, and this parallels the Fgf10 dependence of white adipose tissue formation reported earlier (Asaki et al, 2004;Sakaue et al, 2002). Interestingly, the role of the autocrine or paracrine effect of Fgf10, acting through Fgfr2b, in the development of the white adipose tissue has already been suggested (Ohta and Itoh, 2014). Here, we demonstrate that Fgf10 also signals in an autocrine or paracrine fashion in another mesenchymal and adipocyte-like cell type, the pulmonary LIF.…”

Heterogeneity of adipose tissue in development and metabolic function

“…The ECM serves as a reservoir for various growth factors, such as bone morphogenetic proteins (Margoni et al, 2012;Schulz and Tseng, 2009), fibroblast growth factors (Ohta and Itoh, 2014) and other factors (Muruganandan et al, 2009) known to modulate adipocyte function. Thus, the ECM plays a crucial role in regulating the biophysical properties of tissues and in regulating intracellular signal transduction, either directly via binding to integrins and other proteoglycans or indirectly via regulation of the local microenvironment comprising growth factors, as well as other metabolites and macro-and micronutrients.…”

Fibroblast growth factor-1 (FGF-1) promotes adipogenesis by downregulation of carboxypeptidase A4 (CPA4) – a negative regulator of adipogenesis implicated in the modulation of local and systemic insulin sensitivity

“…There are 22 mammalian FGFs which mediate effects via intracrine (intracellular or autocrine), paracrine and endocrine mechanisms. Of these, three FGFs (two paracrine, FGF-1 and FGF-10, and one endocrine, FGF-21) have been demonstrated to play key roles in the development and structural and metabolic remodeling of adipose tissue (Holland et al 2013, Jonker et al 2012, Ohta and Itoh 2014.…”

“…The importance of coordinated adipose tissue expansion in the maintenance of whole body metabolic homeostasis is well-established (Acosta et al 2016, Henninger et al 2014, Morley et al 2015 and increasing evidence provides a link between the FGF-1 axis and obesity-related adipose tissue remodeling (Jonker et al 2012, Ohta andItoh 2014). Hence, we sought to extend our in vitro observations by exploring the relationship between expression of CPA4 in shAT with indices of adipose tissue and hepatic and muscle insulin sensitivity in a cohort of obese males who had been subject to comprehensive metabolic characterization (Chen et al 2015).…”