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Effects of perilipin (PLIN) gene variation on metabolic syndrome risk and weight loss in obese children and adolescents.

ABSTRACT: Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and metabolic syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multidisciplinary behavioral and nutritional treatment without medication.A total of 234 OCA [body mass index (BMI = 30.4 +/- 4.4 kg/m(2); BMI Z-score = 2.31 +/- 0.4) were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T-->C, PLIN4 11482G-->A, PLIN5 13041A-->G, and PLIN6 14995A-->T).Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkage disequilibrium (D' = 0.999; P < 0.001). At baseline, no anthropometric differences were observed, but minor allele A at PLIN4 was associated with higher triglycerides (111 +/- 49 vs. 94 +/- 42 mg/dl; P = 0.003), lower high-density lipoprotein cholesterol (40 +/- 9 vs. 44 +/- 10 mg/dl; P = 0.003) and higher homeostasis model assessment for insulin resistance (4.0 +/- 2.3 vs. 3.5 +/- 2.1; P = 0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% confidence interval = 1.1-4.9) for genotype GA and 3.5 (95% confidence interval = 1.2-9.9) for AA. After intervention, subjects carrying minor allele T at PLIN6 had increased weight loss (3.3 +/- 3.7 vs. 1.9 +/- 3.4 kg; P = 0.002) and increased loss of the BMI Z-score (0.23 +/- 0.18 vs. 0.18 +/- 0.15; P = 0.003). Due to group size, risk of by-chance findings cannot be excluded.The minor A allele at PLIN4 was associated with higher risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight loss, suggesting that these polymorphisms may predict outcome strategies based on multidisciplinary treatment for OCA.

SUBMITTER: Deram S

PROVIDER: S-EPMC2626445 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Effects of perilipin (PLIN) gene variation on metabolic syndrome risk and weight loss in obese children and adolescents.

Deram Sophie S Nicolau Christiane Y CY Perez-Martinez Pablo P Guazzelli Isabel I Halpern Alfredo A Wajchenberg Bernardo L BL Ordovas Jose M JM Villares Sandra M SM

The Journal of clinical endocrinology and metabolism 20080923 12

<h4>Context</h4>Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and metabolic syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multidisciplinary behavioral and nutritional treatment without medication.<h4>Design</h4>A total of 234 OCA [body mass ind ...[more]

PMID: 18812483

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Project description:To evaluate the effects of an outpatient multidisciplinary weight loss intervention in reducing body mass index (BMI) in children and adolescents suffering overweight and obesity, changes in A Body Shape Index (ABSI, waist circumference normalized to height and weight) and Hip Index (HI, normalized hip circumference) during treatment and correlation between the ABSI and HI with change in BMI z score.We analyze anthropometric data from pediatric patients affected by overweight and obesity aged 2 to 18 years old who entered our multidisciplinary weight loss intervention, which included medical, psychological and nutritional sessions, from January 1st 2006 to December 31st 2016. Lifestyle modification counselling was delivered. Follow-up visits were planned every month for 3 months and subsequently every 2-4 months. BMI, ABSI, and HI were converted to z scores using age and sex specific population normals.864 patients entered our intervention. 453 patients (208 males), mean age 11.2 ±3.1 years, 392 with obesity (86%, z-BMI 2.90 ±0.80 SD) and 61 patients with overweight (z-BMI 1.73±0.21 SD) attended at least 1 follow-up visit. The mean number of visits was 3.5 (± 1.8 SD) in overweight subjects and 3.9 (±2.2 SD) in ones with obesity. At the last attended follow-up visit (at 16 ± 12 months SD) we observed a reduction in mean z-BMI in patients with obesity (to 2.52 ±0.71 SD) and patients with overweight (to 1.46 ±0.5 SD). Most patients (80.8%) reduced their BMI z scores. Mean ABSI and HI z scores showed no significant change. 78/392 patients (19.8%) recovered from obese to overweight, 5/392 (1.2%) from obese to normal weight. The recovery rate from overweight to normal weight was 13.1%. In a multivariate model, initial BMI z score and number of follow-up visits were significant predictors of weight change, while age, sex, ABSI, and HI were not significant predictors.Patients affected by overweight and obesity involved in a multidisciplinary weight loss intervention reduced their mean BMI z score, while ABSI and HI were stable. Weight loss was not predicted by initial ABSI or HI. More visits predict more weight loss, but dropout rates are high. The great majority of patients leave the weight management program before having normalized their BMI.

Project description:Objectives: To evaluate the effect of extreme weight loss programs on circulating metabolites and their relationship with cardiometabolic health in children with metabolic syndrome. Methods: This study was a quasi-experimental design with a pretest and post-test. Thirty children with metabolic syndrome and aged 10-17years were recruited to an extreme weight loss program (i.e., exercise combined with diet control). The primary outcomes included plasma metabolites, body composition, and cardiometabolic risk factors. A total of 324 metabolites were quantitatively detected by an ultra-performance liquid chromatography coupled to tandem mass spectrometry system, and the variable importance in the projection (VIP) value of each metabolite was calculated by the orthogonal projection to latent structures discriminant analysis. The fold change (FC) and p value of each metabolite were used to screen differential metabolites with the following values: VIP>1, p value<0.05, and |log2FC|>0.25. Pathway enrichment and correlation analyses between metabolites and cardiometabolic risk factors were also performed. Result: A large effect size was observed, presenting a weight loss of -8.9kg (Cohen's d=1.00, p<0.001), body mass index reduction of -3.3kg/m2 (Cohen's d=1.47, p<0.001), and body fat percent reduction of -4.1 (%) (Cohen's d=1.22, p<0.001) after the intervention. Similar improvements were found in total cholesterol (Cohen's d=2.65, p<0.001), triglycerides (Cohen's d=2.59, p<0.001), low-density lipoprotein cholesterol (Cohen's d=2.81, p<0.001), glucose metabolism, and blood pressure. A total of 59 metabolites were changed after the intervention (e.g., aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism; nitrogen metabolism, tricarboxylic acid cycle, and phenylalanine, tyrosine, and tryptophan biosynthesis). The changes in metabolites (e.g., amino acids, fatty acids, organic acids, and carnitine) were related to lipid metabolism improvement (p<0.05). Organic acids and carnitines were associated with changes in the body composition (p<0.05). Conclusion: Exercise combined with dietary control improved the body composition and cardiometabolic health in children with metabolic syndrome, and these changes may be related to plasma metabolites.

Dataset Information

Effects of perilipin (PLIN) gene variation on metabolic syndrome risk and weight loss in obese children and adolescents.

Publications

Effects of perilipin (PLIN) gene variation on metabolic syndrome risk and weight loss in obese children and adolescents.

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