Xanthigen is a source of punicic acid and fucoxanthin derived from pomegranate seed and brown seaweed, respectively with recognized triacylglycerol-lowering effects in humans, yet the mechanism remains to be fully elucidated. The present study investigated the inhibitory effects of Xanthigen, fucoxanthin, and punicic acid (70% in pomegranate seed oil) on the differentiation of 3T3-L1 preadipocytes. Xanthigen potently and dose-dependently suppressed accumulation of lipid droplets in adipocytes compared to its individual components, fucoxanthin and pomegranate seed oil. Western blot analysis revealed that Xanthigen markedly down-regulated the protein levels of key adipogenesis transcription factors peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP) β, and C/EBPδ as well as a key enzyme involved in adipogenesis, fatty acid synthase (FAS). Xanthigen up-regulated the NAD(+)-dependent histone deacetylases (SIRT1) and activated AMP-activated protein kinase (AMPK) signaling in differentiated 3T3-L1 adipocytes. In addition, Xanthigen may also stimulate insulin trigger signaling and result in Akt-dependent phosphorylation of forkhead/winged helix O (FoxO)1 and FoxO3a. These results indicate that Xanthigen suppresses adipocyte differentiation and lipid accumulation through multiple mechanisms and may have applications for the treatment of obesity.

Background: The metabolic syndrome (MS) is associated with insulin resistance (IR), a systemic lowgrade inflammatory state and endothelial dysfunction. These disorders may arise at a very early age in obese children. This study aimed to investigate the relationship between endothelial dysfunction and both IR and inflammation in prepubertal obese children. Methods and results: Von Willebrand factor (vWF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured in 46 obese prepubertal children aged 6-9, and in 46 non-obese, ageand sex-matched controls; the possible association of these levels with MS, various inflammatory biomarkers and plasminogen activator inhibitor-1 (PAI-1) was analyzed. Obese children displayed significantly elevated values for sICAM-1 (PZ0.008), vWF (PZ0.034), insulin (PZ0.006), homeostasis model assessment for IR (HOMA-IR; PZ0.003), C-reactive protein (CRP) (P!0.001), PAI-1 (PZ0.002) and leptin (P!0.001). Nonsignificant differences were found in interleukin 6 (IL-6) levels. In the obese group, sICAM-1 showed a positive correlation with insulin (PZ0.013), HOMA-IR (PZ0.015), CRP (PZ0.020), IL-6 (PZ0.023) and PAI-1 (PZ0.015). Corrected for age and sex, insulin, HOMA-IR, IL-6 and CPR were found to be independent predictive factors for sICAM-1. Conclusions: Prepubertal obese children displayed alterations indicative of endothelial dysfunction as well as disorders typical of MS. An association was established between endothelial dysfunction, IR, inflammation and inappropriate fibrinolysis in the children studied.

Background/Aims: The metabolic syndrome (MS) is associated with insulin resistance (IR), inappropriate fibrinolysis and high plasma leptin concentrations. The aim of this study was to quantify fibrinolysis and MS-related variables in obese prepubertal children and to evaluate changes in these variables as a result of improved body mass index (BMI), IR and leptin levels following 9 months of treatment. Methods: The homeostasis model assessment for insulin resistance (HOMA-IR), leptin, plasminogen activator inhibitor-1 (PAI-1) and lipid profile were studied at baseline in obese (n = 50) and nonobese children (n = 50), and after 9 months of treatment in obese children. Results: In the cross-sectional study the mean values for insulin, HOMA-IR, triglycerides, leptin and PAI-1 were significantly higher in obese children than in controls. High-density lipoprotein cholesterol (HDLc) and apolipoprotein A-1 were significantly lower. In the longitudinal study, after 9 months, children with lowered BMI standard deviation score displayed a significant decrease in insulin, HOMA-IR, PAI-1, leptin and triglyceride levels, and an increase in HDLc. Only leptin proved to be an independent predictive factor for changes in PAI-1 (p = 0.010). Conclusion: Obesity-linked disorders appear in obese children prior to puberty; these disorders can be improved by decreasing BMI. Changes in leptin levels were found to independently predict changes in PAI-1 in obese children and can help to diagnose complications associated with the obesity.

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