👤 Nella Polidori

The rs12970134 variant near the melanocortin receptor 4 (MC4-R) has gained relevance suggesting an age dependent phenotypic effect in the induction of obesity in young age. A previous study evaluating 740 Caucasian children has shown this association in prepubertal children older than 8 years. The aim of this study was to assess whether the obesogenic effect of M4CR gene contributed to obesity also in adolescence. After 8 years participants of the original study were contacted and invited to perform an anthropometric evaluation. Out of 35 carriers of the AA risk allele of MC4-R, 12 subjects accepted to participate. Adolescent subjects with the AA risk allele of MC4-R were matched with 24 and 48 subjects, respectively for AG and GG variants. Differences between the three MC4-R genotypes for anthropometric data, for percentage of overweight and obesity and for changes in BMI-SDS over visit have been assessed. At Visit 1 (baseline examination study), the AA risk genotype was confirmed to be associated with higher BMI-SDS (1.3 ± 0.4 vs 0.4 ± 0.1) and waist circumference (66.5 ± 5.8 vs 60.9 ± 7.1) when compared to the GG genotype (p < 0.016 both). At Visit 2 the AA genotype not only was associated with a higher BMI-SDS (1.07 ± 0.5 vs 0.02 ± 0.8) and WC (95.6 ± 13.3 vs 64.9 ± 13.5) when compared to GG genotype, but also when compared to AG genotype (vs 0.5 ± 0.1 and 62.9 ± 10.0, p < 0.016). Whereas AA genotype demonstrated no change of BMI-SDS between visit 1 and visit 2 (p00.32), AG and GG genotype showed a significant reduction (p = 0.01 and 0.001 respectively). Furthermore, a higher percentage of patients were affected by overweight/obesity in the AA genotype compared to AG and GG genotypes (50% vs 20.8% vs 16.5% p = 0.03). This study demonstrates that the rs12970134 variant not only exerts an obesogenic influence in the prepubertal age but remains a major risk factor also during adolescence. Show less

The reaction mechanisms of p-nitrophenyl phosphate hydrolysis catalyzed by two rat liver isoenzymes of the low M(r) phosphotyrosine protein phosphatase (AcP1 and AcP2) were compared. Furthermore, the effect of some heterocyclic compounds on their activities were tested. Cyclic GMP and guanosine causes a particularly high activation of the isoenzyme AcP2, whereas its effect on AcP1 is very poor. A study on the mechanism of cyclic GMP activation was carried out. The results suggest that cyclic GMP activates the AcP2 isoenzyme by increasing the rate of the step that leads to the hydrolysis of the covalent enzyme-substrate phosphorylated complex formed during the catalytic process. The physiological significance of cyclic GMP activation of only one of the two isoenzymes (AcP2) remains uncertain. Show less