Different metabolic responses induced by long-term interdisciplinary therapy in obese adolescents related to ACE I/D polymorphism

Abstract

Introduction: The main purpose of the present study was to investigate whether I/D polymorphism of the ACE gene might affect metabolic changes related to the metabolic syndrome through a long-term interdisciplinary therapy in obese adolescents.

Methods: In total, 125 obese adolescents who entered the interdisciplinary obesity programme were assigned to the following two subgroups: metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and after 1 year. Genomic DNA was extracted from circulating leukocytes.

Results: Subjects with the II genotype in the non-metabolic syndrome group were only to increase their fat-free mass after therapy. Regarding lipid profile, subjects with ID and DD genotypes from both groups reduced their low-density lipoprotein cholesterol levels significantly. The metabolic parameters from the ID and DD genotypes of the non-metabolic syndrome group showed a significantly improved insulin response.

Conclusion: In the present study, we showed that the ACE polymorphism was able to influence the fat-free mass in the I-carry allele in the non-metabolic syndrome group positively. In addition, the I-carry allele was able to improve the insulin resistance of the metabolic syndrome group significantly. These results suggest that the ACE I/D genotypes can influence, in different ways, the specific parameters of metabolism among obese adolescents submitted for long-term interdisciplinary therapy.

Keywords: Interdisciplinary therapy; angiotensin-converting enzyme; metabolic syndrome; obesity; polymorphism.

Figure 1.

The percentage frequencies of the risk determinants of metabolic syndrome in non-metabolic syndrome (n-MS) and metabolic syndrome (MS) groups are divided for angiotensin-converting enzyme (ACE) genotypes. The prevalence altered parameters were obtained according to parameters established by the International Diabetes Federation criteria. HDL: high-density lipoprotein; TG: triglyceride; SBP: systolic blood pressure; DBP: diastolic blood pressure.

Figure 2.

Delta values of body composition in the non-metabolic syndrome (n-MS) and metabolic syndrome (MS) groups by angiotensin-converting enzyme (ACE) I/D genotype. Data are mean±SEM. BMI: body mass index. *P<0.05; **P<0.01.

Figure 3.

Delta values of insulin and homeostasis model assessment–insulin resistance in the non-metabolic syndrome (n-MS) and metabolic syndrome (MS) groups by angiotensin-converting enzyme (ACE) I/D genotype. Data are mean±SEM. *P<0.05; **P<0.01.

Figure 4.

Diagram showing the possible mechanism involved in the difference between the angiotensin-converting enzyme (ACE) I/D polymorphisms affecting the generation of kinin peptide agonists for B2R and B1R in the downstream variation signaling effects. (a) Schematic representation of II/ID genotypes that presented lower ACE concentration, which leads to a decrease of bradykinin degradation and consequently an increase of downstream signaling effects via B2 and B1 receptors. (b) Molecular signaling pathway via B2 and B1 receptor affected by the higher concentration of ACE in DD subjects, which increase the bradykinin degradation consequently reducing the downstream signaling. The pathways highlighted in black in each genotype are supposed to be the more active. BK-(1-5), FFA: fat-free acid; CPN: soluble plasma carboxypeptidase N; CPM: membrane-bound carboxypeptidase M; IR: insulin receptor; B2R: bradykinin B2 receptor; B1R: bradykinin B1 receptor; P: phosphate; IRS1: insulin receptor substrate 1; PI3K: phosphoinositide 3-kinase; AKT: protein kinase B; mTOR: mechanistic target of rapamycin; GLUT4: MAP kinase: mitogen activated protein kinases; iNOS: inducible nitric oxide synthases; l-Arg: l-arginine; NO: oxide nitric; ROS: reactive oxygen species. We have provided references to the boxes of each of the pathways shown.