Visfatin: gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats

Recently, Fukuhara et al. have shown that the novel visfatin is predominantly released from visceral adipocytes and shares metabolic functions with insulin. The authors suggested that there is a relationship between visfatin and the metabolic syndrome in humans. These findings prompted us to clarify the visfatin gene expression from visceral and subcutaneous adipocytes in WOKW rats, as an animal model for polygenically inherited metabolic syndrome, compared to lean Dark Agouti (DA) rats. Moreover, visfatin sequence analysis was performed in WOKW, DA rats, and disease-resistant Fisher 344, Lewis, Brown Norway, and Karlsburg wild rats. The relative gene expression of visfatin displays no significant changes in adipocytes from WOKW rats compared with DA and visfatin sequence analysis of the coding region was identical to the GenBank. But, we found length differences of two repeats, GT and GA, in intron 2 between the strains. In summary, the relative visfatin gene expression is not associated with the metabolic syndrome in WOKW rats.     

Upregulation of fibroblast growth factor-2 by visfatin that promotes endothelial angiogenesis

Adipokines have been known to act as angiogenic regulators in the process of angiogenesis. Recently, we have demonstrated that visfatin, a novel adipokine, has angiogenic activity. However, little has been reported on the underlying mechanism of visfatin-induced angiogenesis. In this study, we report that visfatin-induced angiogenesis is mediated by endothelial fibroblast growth factor-2 (FGF-2). Visfatin increased the levels of FGF-2 mRNA and protein in human endothelial cells. The enhancement in FGF-2 expression was prevented by an inhibitor of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway. Furthermore, visfatin-induced angiogenesis was reduced by inhibition of FGF-2 receptor kinase or by neutralization of FGF-2 function. Taken together, our results indicate that visfatin-induced endothelial angiogenesis is composed largely of two sequential steps: the induction of Erk1/2-dependent FGF-2 gene expression by visfatin and the subsequent FGF-2-induced angiogenesis. These data further suggest an integral role for visfatin-FGF-2 signaling axis in modulating endothelial angiogenesis.     

Beijing ambient particle exposure accelerates atherosclerosis in ApoE knockout mice by upregulating visfatin expression

Ambient particulate matter (PM) exposure has been associated with atherosclerosis. However, research on the effect of real-world exposure to ambient PM in regulating visfatin expression in an animal model is very limited. The objective is to investigate whether Beijing ambient PM exposure could accelerate atherosclerosis in ApoE knockout (ApoE^−/−) mice by upregulating visfatin expression. Forty male ApoE^−/− mice were exposed to untreated ambient air (PM group, n = 20) or filtered air (FA group, n = 20), 24 h/day, 7 days/week, for 2 months. During the exposure, the mass concentrations of PM_2.5 and PM₁₀ in the two groups were continuously monitored. Moreover, a receptor source apportionment model was applied to apportion sources of PM_2.5. At the end of the exposure, visfatin in plasma and aorta, biomarkers of inflammation, oxidative stress and lipid metabolism in blood samples, and bronchoalveolar lavage fluid (BALF) were determined, and the plaque area of the atherosclerosis lesions was quantified. PM-exposed mice were significantly higher than FA-exposed mice in terms of plasma visfatin, OxLDL, MDA, serum TC, LDL, TNF-α as well as IL-6, TNF-α, OxLDL, and MDA in BALF, while SOD and GSH-Px activities in plasma and BALF were reduced in PM-exposed mice. Pathological analysis of the aorta demonstrated that the plaque area and visfatin protein in the PM group increased significantly compared to the FA group. Our findings indicate that ambient PM exposure could accelerate atherosclerosis, which is related to visfatin upregulation, as well as the activation of inflammation and oxidative stress.     

Effects of Visfatin Gene Polymorphism RS4730153 on Exercise-induced Weight Loss of Obese Children and Adolescents of Han Chinese

Visfatin is a recently discovered adipokine that contributes to glucose and obesity-related conditions. This study investigates Visfatin RS4730153 polymorphism from the perspectives of its relations with glucose/lipid metabolism and its influence on the effects of exercise-induced weight loss. Eighty-eight obese Han Chinese children and adolescents were randomly selected from a 2008 Shanghai Weight Loss Summer Camp and were supervised to complete a 4 week aerobic exercise training program. Significant differences were observed in before-exercise TG value and exercise-induced HOMA-β change, with the AG group having a much higher TG value than the GG group (P ≤ 0.05), and the latter exhibiting a significantly larger before-and-after exercise HOMA-β change than the former (P ≤ 0.05). However, no significant difference was observed between the two groups in before exercise indices of body shape, function and quality, nor in exercise-induced changes of body shape, function, and quality. Findings suggest that Visfatin RS4730153 homozygous GG genotype may effect adjustment of glucose and lipid metabolism in obese children and adolescents by reducing TG levels and increasing insulin sensitivity to exercise.