Abstract
Fibroblast growth factors (FGFs) belong to a large family comprising 22 FGF polypeptides that are widely expressed in tissues. Most of the FGFs can be secreted and involved in the regulation of skeletal muscle function and structure. However, the role of fasting on FGF expression pattern in skeletal muscles remains unknown. In this study, we combined bioinformatics analysis and in vivo studies to explore the effect of 24-h fasting on the expression of Fgfs in slow-twitch soleus and fast-twitch tibialis anterior (TA) muscle from male and female C57BL/6 mice. We found that fasting significantly affected the expression of many Fgfs in mouse skeletal muscle. Furthermore, skeletal muscle fibre type and sex also influenced Fgf expression and response to fasting. We observed that in both male and female mice fasting reduced Fgf6 and Fgf11 in the TA muscle rather than the soleus. Moreover, fasting reduced Fgf8 expression in the soleus and TA muscles in female mice rather than in male mice. Fasting also increased Fgf21 expression in female soleus muscle and female and male plasma. Fasting reduced Fgf2 and Fgf18 expression levels without fibre-type and sex-dependent effects in mice. We further found that fasting decreased the expression of an FGF activation marker gene—Flrt2 in the TA muscle but not in the soleus muscle in both male and female mice. This study revealed the expression profile of Fgfs in different skeletal muscle fibre types and different sexes and provides clues to the interaction between the skeletal muscle and other organs, which deserves future investigations.
Highlights
Fibroblast growth factors (FGFs) are a large family of polypeptide growth factors that are widely expressed in organisms ranging from nematodes to humans [1]
Fasting-induced expressions of Fgfs in the skeletal muscle of male mice were analysed using a dataset from NCBI Gene Expression Omnibus (GEO)
Mice were fasted for 24 h and the gastrocnemius skeletal muscles were taken for RNA sequencing experiment [29]
Summary
Fibroblast growth factors (FGFs) are a large family of polypeptide growth factors that are widely expressed in organisms ranging from nematodes to humans [1]. FGFs regulate complex biological functions in vivo and in vitro, including embryogenesis, mitogenesis, cellular migration and differentiation, angiogenesis, In human, the FGF family contains 22 FGF proteins, four FGF receptors (FGFR1-4) [2], and one receptor (FGFR5) lacking an intracellular kinase domain [3]. There is no human FGF15 gene; the gene orthologous to mouse FGF15 is FGF19 [4]. FGFs are classified into three major groups [5]: Canonical FGFs (FGF1-FGF10, FGF16-FGF18, FGF20 and FGF22) can be secreted from cells. Intracrine FGFs (FGF11-FGF14) are not secreted but participate in intracellular processes independent of FGFRs [6]. Hormone-like FGFs (FGF15/19, FGF21 and FGF23) have systemic effects [1, 7]
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