Increased plasma adiponectin concentrations in poorly controlled patients with phenylketonuria normalize with a strict diet: evidence for catecholamine-mediated adiponectin regulation and a complex effect of phenylketonuria diet on atherogenesis risk fact

Adiponectin (Adpn), an adipose tissue-derived hormone, prevents endothelial inflammation and early atherogenesis. Classic phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, results in a reduction of catecholamine biosynthesis and requires treatment with lifelong low-Phe diet to prevent mental dysfunction and allow proper intellectual development. In this study, we evaluated the effect of the quality of PKU diet on plasma Adpn concentrations and related biochemical indices of endothelial dysfunction and atherogenesis. Patients with PKU were divided into groups A (n = 18), who were on a strict diet, and B (n = 18), who were on a loose diet, after evaluation of their 30-day dietetic diaries and measurement of Phe blood concentrations. Twenty healthy children of similar ages and body mass indexes served as controls (group C). Group A patients had normal circulating catecholamines and Adpn and decreased tumor necrosis factor α concentrations and low-density lipoprotein cholesterol/apolipoprotein B ratio compared with groups B and C. Despite these favorable parameters, however, homocysteine concentration was twice as high in group A compared with groups B and C. Interestingly, group B patients under loose dietary control had significantly elevated Adpn concentrations compared with groups A and C and increased tumor necrosis factor α and an unfavorable lipid profile, but normal levels of homocysteine. These data support the hypothesis that catecholamines inhibit Adpn secretion and that the elevated Adpn of the poorly controlled patients might moderate their risk for endothelial dysfunction and atherogenesis. Homocysteine production appears to be unfavorably affected by a strict PKU diet, diverging from the rest of the atherogenesis risk factors, which were improved in the well-controlled patients.