Aim of the study: Akt is involved in upregulating the insulin-signaling pathways essential for maintaining glucose metabolism. Glycosphingolipids are involved in the pathogenesis of glucose intolerance and associated target organ injury. On the other hand, oral administration of β-glucosylceramide (GC) has been shown to alleviate insulin resistance. The present study aimed to determine the effects of oral administration of insulin and GC, separately and in combination, on Akt expression and the subsequent effect on metabolic syndrome characteristics in leptin-deficient mice. Material and methods: Four groups of leptin-deficient ob/ob mice were orally administered for four weeks: vehicle, GC, short-acting insulin, and GC combined with insulin. Mice were followed for hepatic Akt expression and changes in tumor necrosis factor α (TNF-α) level, hyperlipidemia, and liver damage. Results: In mice that received insulin or GC, particularly those that received both, the liver phosphorylation of Akt was significantly increased compared to those that received only vehicle. Serum TNF-α levels decreased in insulin-treated mice. These effects were associated with alleviating glucose intolerance and hyperlipidemia, as manifested by a significant glucose tolerance test improvement and reductions in serum triglyceride and cholesterol levels. Significant liver damage alleviation was noted by liver enzyme reductions in all treated groups, along with liver steatosis in the insulin-treated mice. Conclusions: These data established the potential use of oral insulin administration with glycosphingolipids to alleviate glucose intolerance and associated liver damage and hyperlipidemia via increased Akt expression in the liver. The data support targeting Akt as a potent therapeutic target for metabolic syndrome.
ContextSevere childhood obesity is associated with increased prevalence of cardiometabolic risk factors (CMRFs). Among children with Class 1 obesity, higher BMI may indicate greater cardiometabolic risk. Class 1 obesity reflects a wide spectrum of BMI values. Each 10% increase in BMI above the 95th percentile is equivalent to an average increase of 2.15 kg/m2 and 2.75 kg/m2 in BMI among children and adolescents, respectively. Such increments may be of clinical importance.ObjectivesThe study aimed to determine the prevalence and clustering of CMRFs in children and adolescents with BMI 110%-119% of the 95th BMI percentile.MethodsA cross-sectional analysis of data, from an Israeli health maintenance organization, of children and adolescents (5-17 years) with overweight or Class 1 obesity, and at least one measurement of lipid profile during Jan/2020-May/2021. CMRFs were defined as abnormal lipid profile, elevated alanine aminotransferase, hypertension, and prediabetes or diabetes. Study groups included overweight and Class 1 Obesity-A (BMI < 110%) and Obesity-B (BMI ≥ 110%) of the 95th BMI percentile.ResultsOf 7211 subjects included, 40.2% were overweight, 50.3% obesity-A, and 9.5% obesity-B. Multivariable analyses showed that children and adolescents from the Obesity-B group had increased odds for higher triglycerides, LDL cholesterol, and ALT levels; and lower HDL cholesterol levels, as compared to Obesity-A. The odds of prediabetes (insignificant) tended to be higher in the Obesity-B group, which was associated with increased CMRFs clustering.ConclusionsAmong children and adolescents with Class 1 obesity, BMI ≥ 110% of the 95th percentile was associated with higher prevalence and clustering of CMRFs.
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