Neuropediatrics 2008; 39 - P084
DOI: 10.1055/s-0029-1215853

Peripheral alpha MSH in childhood obesity and craniopharyngioma

HL Müller 1, U Gebhardt 1, T Reinehr 2, PJ Enrion 3, MA Cowley 3 CL Roth 4, für die Studienkommissionen KRANIOPHARYNGEOM 2000/2007
  • 1Zentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg gGmbH, Klinik für Allgemeine Kinderheilkunde, Hämatologie/Onkologie, Oldenburg, Germany
  • 2University of Witten/Herdecke, Vestische Children Hospital, Witten/Herdecke, Germany
  • 3Oregon Health and Science University, Division of Neuroscience, National Primate Research Center, Beaverton, Oregon, United States
  • 4University of Washington, Seattle Children's Hospital Research Institute, Seattle, United States

While the majority of energy homeostasis studies focus on central melanocortin action, peripheral effects of melanocortins and their receptors are not well established. Alpha-melanocyte stimulating hormone (α-MSH) are posttranslational products of the POMC prohormone. The pituitary pars intermedia lobe melanotrophs are considered to be the major source of circulating α-MSH in most mammals. Recent evidence shows that α-MSH plays a role in thermal regulation by increasing free fatty acid oxidation (FAO) and increase of glucose intake in skeletal muscle through the activation of MC5R by activation of the PKA-AMPK pathway.

In this study, we aimed to investigate peripheral α-MSH levels in

  • children with simple obesity

  • lean children,

  • children with hypopituitarism,

  • patients with craniopharyngioma (CP) to learn more about the role of peripheral, human α-MSH in obesity and CP.

Fasting serum α-MSH were measured by a radioimmunoassay with no cross-reactivity to ACTH. Furthermore, we measured fasting leptin, insulin and glucose. Interstingly in patients with hypopituitarism or CP very low to zero α-MSH levels were measured (healthy 26.6 fmol/ml vs. hypopituitarism 8.4 fmol/ml vs. craniopharyngioma 7.7 fmol/ml). Compared to patients with simple obesity, patients with CP showed significantly lower (p<0.001) fasting serum α-MSH levels, but there were no significant differences of α-MSH levels in obese children compared to lean children. Low α-MSH levels in CP did not increase one hour after ingestion of a 500kcal mixed liquid meal. CP patients had higher fasting insulin, insulin resistance index HOMA and leptin levels compared to patients with simple obesity and similar BMI.

The low serum α-MSH levels in patient groups, which have low- or non-functioning pituitaries, verify that the pituitary is the critical source for circulating α-MSH. The very low α-MSH levels in CP can be explained by their pituitary or hypothalamic damage and might contribute to severe obesity associated with low thermogenesis.

Supproted by Deutsche Kinderkrebsstiftung, Bonn, Germany.