Serum alpha-melanocyte-stimulating hormone (a-MSH), brain-derived neurotrophic factor (BDNF), and agouti-related protein (AGRP) levels in children with Prader-Willi or Bardet-Biedl syndromes

Although leptin/melanocortin pathway pathologies in hypothalamus are thought to be the main cause of early-onset obesity and hyperphagia in PWS and BBS, the exact mechanism is still not known.To measure serum concentrations of a-MSH, BDNF and AGRP in a group of children with BBS or PWS.We recruited 12 subjects with PWS, 12 subjects with BBS, 28 obese controls (OC) and 26 lean controls (LC) matched for age, sex and puberty. Serum a-MSH, BDNF and AGRP levels were measured by the ELISA method.The mean a-MSH level was lower in PWS than those of OC and LC (3729 ± 1319, 5211 ± 829 and 5681 ± 565 pg/ml, respectively, p < 0.001), and mean a-MSH was lower in OC than LC (p < 0.05). The mean BDNF level of PWS was higher than those of OC and LC (565 ± 122, 482 ± 102 and 391 ± 74 pg/ml, respectively, p < 0.001). On the other hand, mean a-MSH level of BBS was lower than those of OC and LC (4543 ± 658, 5211 ± 829 and 5681 ± 565 pg/ml, respectively, p < 0.001), and mean a-MSH was lower in OC than LC (p < 0.05). The mean BDNF level of BBS was higher than those of OC and LC (583 ± 115, 482 ± 102 and 391 ± 74 pg/ml, respectively, p < 0.001). Additionally, both in PWS and BBS, the mean BDNF level was higher in OC than LC (p < 0.01). Regarding AGRP level, there was no difference both in BBS and PWS compared to OC.We found that the serum a-MSH levels of PWS and BBS groups are significantly lower compared to those of obese and lean controls. Therefore, we can speculate that the circulating a-MSH level does properly reflect its central production, and the serum a-MSH level might be a good biomarker to detect a-MSH deficiency in individuals suspected to have BBS or PWS, and also in those with POMC, PCSK1, and LEPR deficiency.