BackgroundHepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD.MethodsThe prospective study included 80 obese children (aged 7–17 years, median 12 years) admitted to our Department to diagnose initially suspected liver disease. Patients with viral hepatitis (HCV, HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson’s disease, alfa-1–antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD was diagnosed based on pediatric diagnostic criteria in obese children with liver steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum activity after exclusion of other major liver diseases listed before. Ultrasonography was used as a screening method and for qualitative assessment of the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis was defined as a score > 1. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1HMRS) which is the most accurate technique for assessment of ectopic fat accumulation. Fasting serum concentration of ceramides was measured in 62 children.ResultsNAFLD was diagnosed in 31 children. Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic, palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p = 0.006, respectively) in children with NAFLD compared to controls (n = 14). Moreover, children with NAFLD had significantly higher activity of ALT (p < 0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in 1HMRS (p < 0.001) compared to children without NAFLD. We did not find significant differences in total and FA-ceramide species concentrations between children with mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2–3).ConclusionElevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.
Introduction Interleukin-18 (IL-18) is a proinflammatory cytokine associated with metabolic syndrome (MS). Nonalcoholic fatty liver disease (NAFLD) can be recognized as a feature of MS. Material and Methods Serum IL-18 concentration was evaluated in serum of 108 obese children, determined with ELISA, and referred to degree of liver steatosis in USG or total intrahepatic lipid content assessed by magnetic resonance proton spectroscopy (1HMRS). Results Fatty liver was confirmed in 89 children with USG and in 72 with 1HMRS. IL-18 concentration demonstrated significantly higher values in patients than in controls. Significant correlations between IL-18 and ALT, GGT, triglycerides, hsCRP, and the degree of liver steatosis were demonstrated. NAFLD children had significantly higher level of IL-18, ALT, GGT, HOMA-IR, waist circumference, and total lipids content in 1HMRS than other obese children. IL-18 level was also significantly higher in obese children with advanced liver steatosis. Measurement of serum IL-18 showed ability to differentiate children with fatty liver from those without steatosis. Conclusion Elevated serum IL-18 concentration and its correlation with hepatocyte injury, systemic inflammation, and degree of liver steatosis support role in NAFLD pathomechanism. IL-18 can be considered to play a role in predicting advanced liver steatosis and fatty liver in obese children.
BackgroundEctopic hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of non-alcoholic fatty liver disease (NAFLD). The current study has shown that fat tissue constitutes an important endocrine organ with its own production and metabolism of many biologically active substances, among which adipokines play an important role. Classic adipokines (e.g. leptin, adiponectin, resistin) are fat-derived hormones which serum level is altered in patients with NAFLD. The role of novel adipokines in the pathomechanism of this disease is not clear. Therefore, the aim of our study was to evaluate the serum concentrations of chemerin, omentin and vaspin in obese children with NAFLD.MethodsForty-five obese children, aged 7–17 years old, were admitted to our Department with suspected liver disease (hepatomegaly, and/or ultrasonographic liver brightness, and/or increased ALT activity). Viral hepatitides, as well as autoimmune and metabolic liver diseases were excluded. Fasting serum levels of chemerin, omentin and vaspin were determined. The grade of liver steatosis in ultrasound was graded according to Saverymuttu. 1HMR spectroscopy was performed with a 1.5 T scanner and with PRESS sequencing.ResultsFatty liver was confirmed in 39 children by ultrasound and in 33 patients by 1HMRS (19 of them also had increased ALT activity /NAFLD/). Chemerin and vaspin levels were significantly higher in children with NAFLD compared to the control group (n = 30). The concentration of chemerin was significantly higher in children with advanced liver steatosis compared to non-hepatopathic patients (p = 0,02). Significant positive correlations were found between the total liver lipids in 1HMRS and chemerin (r = 0,33; p = 0,02) and vaspin (r = 0,4; p = 0,006). The ability of serum chemerin (cut-off = 190 ng/ml, Se = 75%, Sp = 58%) to differentiate children with fatty liver in 1HMRS from those without steatosis was significant (AUC = 0,7, p = 0,04). Omentin and vaspin did not allow a useful prediction to be made.ConclusionChemerin seems to be the most suitable non-invasive biomarker in predicting both intrahepatic lipid content in obese children and advanced liver steatosis in children with NAFLD.
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