No abstract

Serum SFRP5 is regulated by weight status and seems to be correlated with metabolic disorders in children.

The aim was to clarify the associations of five adipocytokines: Sfrp5, Wnt5a, adiponectin, chemerin and high-sensitivity C-reactive protein (hsCRP) with blood pressure (BP), and to examine whether BP can be influenced by changes in these adipocytokines in obese children after a 6-month lifestyle intervention. We conducted a cross-sectional study in 263 obese children and performed a 6-month lifestyle intervention in a subgroup of 89 obese children with hypertension. Anthropometric data, adiponectin, chemerin, Sfrp5 and Wnt5a were assessed at baseline and after 6-month lifestyle intervention. Sfrp5 and adiponectin serum levels were significantly lower in obese children with hypertension, but Wnt5a, hsCRP and chemerin serum levels were elevated in obese children with hypertension. In multivariable linear regression analysis, Sfrp5, Wnt5a, adiponectin, chemerin and hsCRP were associated with both standard deviation score-systolic blood pressure (SDS-SBP) and -diastolic blood pressure (SDS-DBP). Lifestyle intervention resulted in a significant improvement in BP and weight loss. These were accompanied by significant decreases in hsCRP and chemerin, and significant increases in Sfrp5 and adiponectin, whereas Wnt5a was not changed. Furthermore, the changes in Sfrp5 and adiponectin act as partial mediators of the relationship between weight loss and BP reduction after controlling for covariates. Although Sfrp5, Wnt5a, adiponectin, chemerin and hsCRP levels are correlated with BP at baseline, after lifestyle intervention, the relationship between weight loss and BP reduction were partially mediated by changes in Sfrp5 and adiponectin after controlling for covariates. So we speculate that Sfrp5 and adiponectin may have some influence on BP.

Previous studies reported that Stat5 promotes adipogenesis and white adipocyte differentiation. However, the role of Stat5 in brown adipocyte development is poorly understood. We found Stat5a was higher expressed in brown adipocytes than in white adipocytes, and its level was increased during the process of brown adipocyte differentiation. In addition, Stat5a expression was affected by cold stress and high-fat diet-feeding, suggesting a potential role in thermogenesis. Knockdown of Stat5a induced downregulation of brown fat specific genes (UCP1, PGC-1α, Acox-1 and Cidea), while overexpression of Stat5a did the opposite effect. What is more, bioinformatics analysis, ChIP assay and Luciferase activity assay all verified that Stat5a directly bind and transactivate Kdm6a promoter (Lysine-specific demethylase 6A). Further, we found that Stat5a overexpression promoted the expression of Kdm6a and inhibited the trimethylation of H3K27. While inhibiting of Kdm6a reversed the promoting effect of Stat5a overexpression on the expression of brown fat specific genes. Therefore, we conclude that Stat5a participated in brown adipocyte differentiation and thermogenic program through binding and transactivating the Kdm6a promoter.

This study investigated the effects of Wnt5a/caveolin/JNK signaling pathway and SFRP5 protein on ox-LDL-induced apoptosis of HUVEC cells. The difference of serological indexes between healthy average weight and obese children and the expression of Wnt 5a and SFRP5 was detected by clinical examination, and the correlation between serum SFRP5, Wnt 5a and the vascular endothelial injury was detected. HUVEC cells were induced by ox-LDL to construct an endothelial injury model, siRNA-transfected cells were used to construct down-regulated SFRP5 and Wnt 5A expression groups, and recombination methods were used to construct up-regulated Wnt5a and SFRP5 expression groups. The expression of Wnt 5a, caveolin-1, JNK and apoptosis-related proteins under different treatments were detected by the Western blot method, and apoptosis was detected by flow cytometry. Serological results showed that the level of Sfrp5 in obese children was significantly lower than that in healthy children, and the level of Wnt5a was significantly higher than that in healthy children. Moreover, Ln Sfrp5 was significantly negatively correlated with Ang-2 in blood circulation, ICAM-1 and E-selectin selectin, but not with VCAM-1. When Wnt5a was up-regulated, the expression of caveolin-1 and JNK increased significantly, Bcl-2 decreased significantly, and the apoptotic rate increased significantly. Nevertheless, when Sfrp5 expression was up-regulated, the result was the opposite. SFRP5 and Wnt5a are involved in the vascular endothelial injury. Wnt5a can promote apoptosis of HUVEC cells through Wnt5a/JNK/Caveolin-1 pathway, while SFRP5 can inhibit apoptosis by interfering with this pathway.