Association of Secreted Frizzled-Related Protein 4 with Obesity and Type II Diabetes

Abstract

Secreted frizzled-related protein 4 (SFRP4) is secreted protein family member similar to the sequence of frizzled receptors of wingless-related integration site (Wnt) signaling pathways which regulate various functions from fetal growth to adulthood. SFRPs are recognized as opponents of Wnt signaling and are thought to be affiliated with Wnts. Further research revealed their interaction with frizzled receptors and functional differences were transferred to these proteins, the power of Wnt signaling without flexibility. Also, SFRP4 is linked to many diseases including obesity, type 2 diabetes (T2D), and cancer. In addition, SFRP4 acts as a biomarker for the diagnosis of T2D and its expression is observed before the clinical diagnosis of T2D. This review is mainly focused on the role of SFRP4 in obesity and its role in β-cell failure that leads to T2D. SFRP4 acts on adipose tissue that causes increased production of adipokines which creates oxidative stress in the pancreas with low levels of antioxidant enzymes in pancreatic β-cells resulting in failure of insulin exocytosis. Inflammation caused by obesity is an important factor in the pathogenesis of insulin resistance and metabolic syndrome. Pro-inflammatory cytokines may induce insulin resistance in adipose tissue, bone tissue and liver by blocking the transmission of insulin signals. SFRP4 secretion is caused by interleukin 1-β (IL1-β).This review also highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding the cellular pathway and identifying SFRP4 may help to eliminate or reduce the chances of developing T2D.