The Frequent Adiponutrin (PNPLA3) Variant p.Ile148Met Is Associated with Early Liver Injury: Analysis of a German Pediatric Cohort.

Introduction. The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury. Here, we investigate the association of this polymorphism with hepatic and metabolic traits in a pediatric cohort. Patients and Methods. The study cohort comprised 142 German children (age 5-9 years, 98 overweight, 19 children with NAFLD). Results. Overweight children presented with increased serum ALT (P = 0.001) and GGT (P < 0.001) activities. ALT activities differed significantly (P = 0.02) between carriers of different PNPLA3 genotypes in the entire study cohort, in normal weight children (P = 0.02) and in children younger than 7 years (P = 0.02). Carriers of the prosteatotic PNPLA3 genotype p.148Met/Met displayed higher ALT activities as compared to children with the frequent genotype p.148Ile/Ile (P = 0.01). The BMI was however a stronger predictor of ALT activities compared to the PNPLA3 genotype (P < 0.001 and P = 0.06, resp.). The variant was associated with increased serum glucose levels (P = 0.01) and HOMA index (P = 0.02) in carriers of the p.148Ile/Met genotype but did not affect other metabolic traits or the presence of NAFLD. Discussion. The frequent PNPLA3 variant p.Ile148Met is associated with serum ALT activities already at a young age.

Differences in the prevalence of metabolic disorders between prepubertal boys and girls from 5 to 8 years of age.

AIM: To determine the prevalence of metabolic abnormalities, and differences between the sexes, in prepubertal overweight and normal weight children aged from 5 to 8 years, without any signs of health impairments or metabolic disturbances at the time of recruitment. METHODS: General health status and inflammatory markers were assessed in 100 overweight and 51 normal weight children, who were living in Germany and had undergone mandatory medical examinations. The study comprised of 81 girls and 70 boys. RESULTS: Despite being recruited as healthy, 73% of the overweight children and 16% of the normal weight children were found to suffer from one or more metabolic abnormalities, such as hypertension or insulin resistance. Girls with a body mass index (BMI) percentile of ≥80th showed an increased susceptibility to metabolic disorders, and a similar effect was found for boys with a BMI percentile of ≥95th. Plasma levels of proinflammatory markers, such as plasminogen activator inhibitor-1 and leptin, were also significantly higher in overweight than normal weight children. CONCLUSION: Metabolic and cardiovascular abnormalities and pro-inflammatory markers were prevalent in overweight prepubertal children. The prevalence rates appeared to differ between the sexes.

Dietary pattern and leisure time activity of overweight and normal weight children in Germany: sex-specific differences.

BACKGROUND: Several studies indicate that dietary pattern and leisure time activities of adults not only differ between sexes but also between overweight and normal weight individuals. The aim of the present study was to determine if sex-specific differences in dietary pattern and leisure time activity already exist and are associated with weight status in young childhood. METHODS: Nutritional intake, anthropometric parameters, leisure time activities and socio- demographical factors were assessed in 100 overweight and 51 normal weight children (81 girls and 70 boys), aged 5-8 years. RESULTS: In general, independent of body weight, boys ate more cheese while girls consumed more vegetables and spent more time with sedentary activities. Moreover, regardless of sex, total energy and macronutrient intake did not differ between normal weight and overweight children. Also, time spent with sportive activities did not differ between groups; however, overweight boys spent significantly more leisure time with sedentary activities than normal weight boys. Furthermore, BMI of mothers and time spent with sedentary activities were identified as independent risk factors for the development of overweight when performing multiple regression analyses. CONCLUSIONS: Taken together, results of our study suggest that already at young age sex influences dietary pattern independent of body weight. Furthermore, an increased time spent with sedentary activities and an elevated maternal BMI were found to be associated with an elevated body weight in children. ( TRIAL REGISTRATION: NCT01306396).

A moderate weight reduction through dietary intervention decreases hepatic fat content in patients with non-alcoholic fatty liver disease (NAFLD): a pilot study.

PURPOSE: As a diet rich in fructose and an impaired intestinal barrier function have been proposed to be risk factors for the development of non-alcoholic fatty liver disease (NAFLD), the aim of the present pilot study was to determine whether a dietary intervention focusing on a reduction of fructose intake (-50 % in comparison with baseline) has a beneficial effect on liver status. METHODS: A total of 15 patients with NAFLD were enrolled in the study of which 10 finished the study. Fructose and total nutrient intake were assessed using a diet history. At baseline and after 6 months liver status and markers of intestinal barrier function as well as plasminogen activator inhibitor (PAI-) 1 concentration were determined in plasma. RESULTS: Hepatic lipid content and transaminases in plasma as well as body mass index and some parameters of glucose metabolism (e.g., fasting plasma insulin) were significantly lower at the end of the intervention when compared to baseline. Whereas the dietary intervention had no effect on the prevalence of bacterial overgrowth, orocecal transit time and the intestinal permeability or blood ethanol levels endotoxin and PAI-1 concentration in plasma were significantly lower at the end of 6 months intervention period than at baseline. CONCLUSIONS: Taken together, our results indicate that a dietary intervention focusing only on one dietary parameter like fructose may help to decrease intrahepatic fat content of NAFLD patients.

Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease (NAFLD).

BACKGROUND: A role of an altered dietary pattern (e.g., a diet rich in sugar) but also alterations at the level of the intestinal barrier have repeatedly been discussed to be involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). AIMS: To determine if the nutritional intake, intestinal flora, and permeability and the development of NAFLD are related in humans. METHODS: Ten controls and 20 patients with NAFLD ranging from simple steatosis to steatohepatitis were included in the study. Bacterial overgrowth, orocecal transit time, and intestinal permeability were assessed. Alcohol, endotoxin, and plasminogen activator inhibitor (PAI-) 1 concentration were determined in plasma. Nutritional intake was assessed using a dietary history. RESULTS: Despite no differences in the prevalence of bacterial overgrowth and in the orocecal transit time, intestinal permeability, alcohol, and endotoxin levels in plasma were significantly higher in patients with NAFLD than in controls. Similar results were also found for PAI-1 plasma concentrations. Patients with NAFLD had a significantly higher intake of protein, total carbohydrates, and mono- as well as disaccharides than controls. PAI-1, endotoxin, and ALT plasma levels were positively related to total protein and carbohydrate intake. CONCLUSIONS: Taken together, our results indicate that intestinal permeability, endogenous alcohol synthesis, and nutritional intake are markedly altered in patients with NAFLD.

A low fructose diet in the treatment of pediatric obesity: a pilot study.

BACKGROUND: Over the last three decades the prevalence of overweight and obesity has increased dramatically among children and adolescents worldwide. As the results of animal and human studies suggest that a diet rich in fructose may be a risk factor for the development of overweight, the aim of the pilot study was to evaluate if a dietary counseling aimed at a moderate reduction of dietary fructose intake (-50% in comparison to intake at baseline) has a positive effect on the body mass index (BMI) of overweight and obese children. METHODS: Fifteen overweight or obese children aged 5-8 years were included into the 3 month dietary intervention study. At baseline and after 4 and 8 weeks children and their parents were trained to reduce fructose in the children's diet. Anthropometric parameters for calculating BMI and BMI standard deviation scores (BMI-SDS) as well as nutritional intake were assessed at baseline, after the 12-week intervention and after 12 week of follow up. RESULTS: After the 12-week intervention children had significantly reduced their total energy, fructose, sucrose and glucose intake. BMI and BMI-SDS were significantly reduced by 0.68 kg/m(2) and 0.21, respectively, at the end of the intervention. At follow up, the BMI-SDS was significantly lower in comparison to baseline while the BMI was only decreased by trend (P= 0.08). CONCLUSIONS: The results of our pilot study indicate that counseling aimed towards a moderate reduction of dietary fructose and/or general sugar intake may have a positive effect on BMI in overweight and obese children.