Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans.

AIMS: The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. METHODS: A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. RESULTS: No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. CONCLUSIONS: In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.

Effects of aldehydes on CD36 expression.

INTRODUCTION: During the oil frying process lipid peroxidation compounds are formed. These products can modulate gene expression and alter cellular behaviour. The cellular uptake of oxidized LDL, a key step in the development of atherosclerosis, is mediated by the CD36 scavenger receptor, whose expression is down-regulated by alpha-tocopherol. OBJECTIVE: To determine the effects of water-soluble aldehydes, obtained from thermally oxidized sunflower oil on the expression of CD36 scavenger receptor in human monocytes (THP-1 cells). We also wanted to study the effects of alpha-tocopherol on CD36 expression in the presence of water-soluble aldehydes. MATERIALS AND METHODS: Sunflower oil was heated in a frying pan, at 180--200 degrees C for 40 min, water-soluble aldehydes were isolated, and the content of thiobarbituric acid reacting substances (TBARS) was determined. THP-1 monocytes were cultured in RPMI medium during 24 h and incubated with increasing concentrations of the water-soluble aldehydes (ranging from 0.05 to 1 microM) and with or without 50 microM of alpha-tocopherol. In parallel, THP-1 cells were cultured with the same volume of an extract obtained from non-oxidized oil or distilled water. The CD36 expression at the cell surface was studied with fluorescence-activated cell sorting (FACS). RESULTS: Monocytes incubated in a medium containing water-soluble aldehydes, showed a dose dependent increase in the expression of the CD36 protein on the cell surface, compared to with the control groups. When the cells were treated simultaneously with 50 microM of alpha-tocopherol a significant reduction in the expression of the CD36 protein was observed. CONCLUSION: Water-soluble aldehydes, extracted from thermally oxidized culinary oil, increase the expression of CD36. This effect is partially decreased by the presence of alpha-tocopherol.

[Metabolic alterations related to syndrome X and low vitamin E levels in obese children with acanthosis nigricans]. / Alteraciones relacionadas con el síndrome X y bajos niveles de vitamina E en niños con obesidad y acantosis nigricans.

BACKGROUND: In adults, both metabolic alterations related to syndrome X and lower plasma vitamin E levels have been associated with an increased risk of developing cardiovascular disease. OBJECTIVES: To study the presence of metabolic alterations related to syndrome X and to determine the plasma levels of vitamin E in obese children with acanthosis nigricans. METHODS: We performed a prospective study in 42 obese children [15 with acanthosis nigricans (AN) and 27 without]. Thirteen healthy non-obese children were also studied. After a 12-hour fast, plasma levels of glucose, insulin, triglycerides, cholesterol, high-density lipoprotein (HDL)-cholesterol, and vitamin E were determined. The insulin resistance index was also calculated. Differences between groups were determined using ANOVA. RESULTS: Obese children with AN showed higher plasma levels of insulin and triglycerides and lower plasma levels of HDL-cholesterol and vitamin E, as well as a higher insulin resistance index than non-obese children and obese children without AN. CONCLUSIONS: In obese children, the presence of acanthosis nigricans is linked to a group of metabolic alterations associated with a higher risk of developing cardiovascular disease and type 2 diabetes.

Alteraciones relacionadas con el síndrome X y bajos niveles de vitamina E en niños con obesidad y acantosis nigricans / Metabolic alterations related to syndrome X and low vitamin E levels in obese children with acanthosis nigricans

Antecedentes: En adultos, tanto las alteraciones metabólicas asociadas al síndrome X, como la disminución en las concentraciones plasmáticas de vitamina E, se han asociado a un mayor riesgo de desarrollar enfermedades cardiovasculares. Objetivos: Estudiar en niños obesos con acantosis nigricans la presencia de alteraciones metabólicas relacionadas con el síndrome X y determinar las concentraciones plasmáticas de vitamina E. Métodos: Se llevó a cabo un estudio prospectivo en 42 niños obesos, 15 con acantosis nigricans (OB+AN) y 27 sin ella (OB-AN), y 13 niños sanos sin obesidad. En todos ellos, y tras 12 h de ayuno, se determinaron las concentraciones plasmáticas de glucosa, insulina, vitamina E, triglicéridos, colesterol y colesterol HDL. Se calculó el índice de resistencia a la insulina. Las diferencias entre grupos se determinaron mediante el análisis de la varianza. Resultados: Los niños obesos con acantosis nigricans presentaron mayores concentraciones de insulina plasmática y de triglicéridos, menores niveles de colesterol HDL (lipoproteínas de alta densidad) y de vitamina E en plasma, así como un índice de resistencia a la insulina más elevado que los niños obesos sin acantosis nigricans o que los valores observados en un grupo de niños sin obesidad. Conclusiones: La presencia de acantosis nigricans en niños obesos define a un grupo de niños con alteraciones metabólicas asociadas a un mayor riesgo de desarrollar enfermedades cardiovasculares y diabetes de tipo 2 (AU)

Effect of acipimox on plasma lipids and glucose/insulin in pregnant rats.

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (i.v.) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.