Abstract
Various reports have suggested that secreted frizzled-related protein (SFRP) 5 (SFRP5) plays a regulatory role in the processes of cellular proliferation and differentiation, by means of inactivating the Wnt/β-catenin signaling pathway. Recently, SFRP5 has been identified as an anti-inflammatory adipokine, which may be induced during preadipocyte proliferation, differentiation, and maturation. This review aims to identify the recent progress in the research and development of SFRP5 that can play a role in influencing lipid metabolism, inflammation, and type 2 diabetes mellitus (T2DM). Recent evidence has indicated that SFRP5 is capable of stimulating adipocyte differentiation via inhibition of the Wnt/β-catenin signaling pathway. In addition, SFRP5 binding with wingless-type murine mammary tumor virus integration site family, member 5A (Wnt5a), inhibits the activation of c-Jun N-terminal kinase (JNK) downstream of the Wnt signaling pathway. An antagonistic relationship has been found between the reductions in inflammatory cytokine production and serine phosphorylation of insulin receptor substrate-1 (IRS-1) in regard to inhibition of insulin signaling network. By this mechanism, SFRP5 exerts its influence on metabolic function. Based on our review of the current available literature, we support the notion that SFRP5 can be used as a therapeutic target in the treatment of T2DM.
Highlights
Secreted frizzled-related proteins (SFRPs) consist of five identified secreted glycoproteins, which have been identified as negative modulators of the Wnt signal transduction pathway [1,2]
SFRP5 has been reported to exert its effects by regulating the Wnt signal transduction, by competing with membrane frizzled receptors that function as a binding domain for secreted Wnt ligands [7]
Christodoulides et al [13] reported that SFRP5-mediated epigenetic silencing of the Wnt signaling pathway in white adipose tissues could lead to strengthened adipogenesis with a significant likelihood increasing susceptibility to diet-induced obesity in mice models
Summary
Secreted frizzled-related proteins (SFRPs) consist of five identified secreted glycoproteins, which have been identified as negative modulators of the Wnt signal transduction pathway [1,2]. Christodoulides et al [13] reported that SFRP5-mediated epigenetic silencing of the Wnt signaling pathway in white adipose tissues could lead to strengthened adipogenesis with a significant likelihood increasing susceptibility to diet-induced obesity in mice models.
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