Differential Patterns of Secreted Frizzled-Related Protein 4 (SFRP4) in Adipocyte Differentiation: Adipose Depot Specificity

Abstract

Background/Aims: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that acts as soluble modulators of Wnt signaling. Given the substantial rise in obesity, depot-specific fat accumulation and its associated diseases like diabetes, it is important to understand the molecular basis of depot-specific adipocyte differentiation. In the current study, we investigated the expression of SFRP4 in both subcutaneous and visceral adipose tissue in terms of their differentiation. Methods: White preadipocytes were isolated from the inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) from C57BL/6J mice (age: 8-week-old, male). SFRP4 expression in iWAT and eWAT preadipocytes was silenced by siRNA transfection and harvested cells for gene and protein expression analysis was performed during the differentiation. Furthermore, iWAT and eWAT preadipocytes treated with or without IL-1β were harvested for gene and protein expression analysis. Results: SFRP4 expression levels were gradually increased and proportionally associated with eWAT adipocyte differentiation toward maturation at 14 days, while iWAT adipocyte just showed an opposite tendency. Moreover, genetic (adiponectin, C/EBPα, C/EBPβ, FABP4, GLUT4 and PPARγ) analysis demonstrated that depot-specific adipogenesis in response to SFRP4 silencing in eWAT and iWAT preadipocytes. Upon IL-1β treatment, SFRP4 mRNA expression decreased significantly in iWAT adipocyte, but the expression was no significant difference in eWAT adipocyte. Conclusion: These results suggest that SFRP4 expression differentially mediates adipocyte differentiation and may play an important role in adipogenesis.

lncRNAS56464.1 as a ceRNA promotes the proliferation of fibroblast‑like synoviocytes in experimental arthritis via the Wnt signaling pathway and sponges miR‑152‑3p

“…SFRP4 is a secretory protein with a size of 40 kDa, consisting of more than 300 amino acids (76). It can inhibit the activation of the Wnt signaling pathway by competitively binding with receptors related to the Wnt signaling pathway.…”

Secreted frizzled‑related protein 4 promotes brown adipocyte differentiation

“…In addition, bioinformatics data analysis showed that the Secreted frizzled-related protein 4 promotes brown adipocyte differentiation expression level of SFRP4 in fat tissue of obese pigs was significantly higher compared with that of lean pigs (12). Thirdly, previously published research findings demonstrated that the expression pattern and function of SFRP4 has adipose tissue depot specificity in subcutaneous and visceral adipose tissue in mice (13). However, little is known about the role and function of SFRP4 in the formation and thermogenesis of BAT which plays an important role in lipid metabolism, obesity and energy consumption (4).…”

“…The number of transcripts was quantified, and each sample was normalized according to its b-actin content. Relative expression of the gene of interest (GOI) was determined using calculation=2 (Cq β-actin gene-Cq GOI) (13). PCR primer sequences are shown in Table SI.…”

Secreted frizzled‐related protein 4 and its implication in obesity and type‐2 diabetes

“…It has been reported that SFRP4 is overexpressed during differentiation of preadipocytes to mature adipocytes as obese animals have more expression of SFRP4 as compared to lean animals . Differentiation of preadipocytes to adipose tissues in humans is affected by SFRP4 and SFRP4 overexpression leads to the elevation in lipid accumulation . The SFRP4 expression in adipose tissues of obese individuals was increased and is associated to insulin resistance …”

“…Adipogenesis is stimulated by SFRP1, SFRP2, and SFRP4 in both human and murine models . SFRP4 has been described to be involved in metabolism of glucose and lipids by interacting Wnt ligands and its level in obesity are increased . In undifferentiated cells, SFRP4 expression level is higher but with the progress of differentiation, its level is decreased.…”