Alpha-Melanocyte-Stimulating Hormone and Agouti-Related Protein: Do They Play a Role in Appetite Regulation in Childhood Obesity?

Objective: The hypothalamus plays a crucial role in the regulation of feeding behavior. The anorexigenic neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) and the orexigenic neuropeptide agouti-related protein (AgRP) are among the major peptides produced in the hypothalamus. This study investigated the plasma concentrations of alpha-MSH and AgRP in underweight and obese children and their healthy peers. The associations between alpha-MSH and AgRP levels and anthropometric and nutritional markers of malnutrition and obesity were also assessed. Methods: Healthy sex-matched subjects aged 2 to 12 years were divided into 3 groups, as underweight (n=57), obese (n=61), and of normal weight (n=57). Plasma fasting concentrations of alpha-MSH and AgRP were measured by enzyme-linked immunosorbent assay. The differences between the three groups as to the relationships between plasma concentrations of alpha-MSH and AgRP and anthropometric data, serum biochemical parameters and homeostatic model assessment of insulin resistance were evaluated. Results: Obese children had significantly lower alpha-MSH levels than underweight (1194 +/- 865 vs. 1904 +/- 1312 ng/mL, p=0.006) and normal weight (1194 +/- 865 vs. 1762 +/- 1463 ng/mL, p=0.036) children; there were no significant differences in the alpha-MSH levels between the underweight and normal weight children (p=0.811). Also, no significant differences were observed between the underweight and obese children regarding the AgRP levels (742 +/- 352 vs. 828 +/- 417 ng/mL, p=0.125). We found a significant positive correlation between plasma alpha-MSH and AgRP levels across the entire sample. Conclusion: This study is the first to demonstrate body weight-related differences in a-MSH and AgRP levels in children. Circulating plasma alpha-MSH levels in obese children were markedly lower than those of underweight and normal-weight children. This suggests that a-MSH could play a role in appetite regulation.