Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: sex differences and the role of growth hormone.
OBJECTIVE
To identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment.


METHODS
We compared amino acids, fatty acids and acylcarnitines in GH-treated and untreated PWS children and obese and lean controls to identify biomarkers associated with ghrelin, peptide YY and markers of insulin sensitivity (adiponectin and HOMA-IR).


RESULTS
Compared with obese controls (OC), children with PWS had fasting hyperghrelinaemia, hyperadiponectinaemia, hypoinsulinaemia and increased ghrelin/PYY. Hyperghrelinaemia, hyperadiponectinaemia and hypoinsulinaemia were more striking in PWS females than males, and decreases in BCAA were detected only in PWS females. GH-treated PWS subjects had lower leptin and higher IGF-1 and adiponectin than untreated subjects; fasting ghrelin, PYY and insulin levels were comparable. Ghrelin correlated inversely with BCAA in PWS but not OC. Adiponectin correlated negatively with BMIz and HOMA-IR in PWS; in contrast, adiponectin correlated more strongly with BCAA than BMIz or HOMA-IR in OC.


CONCLUSIONS
BCAA levels were lower in PWS females than OC females and correlated inversely with ghrelin. Low BCAA in PWS females may promote hyperghrelinaemia and hyperphagia, while hyperadiponectinaemia may maintain insulin sensitivity despite excess weight gain. GH treatment may reduce leptin and increase adiponectin, but does not affect fasting ghrelin or PYY.
Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, NC, USA.
Krystal A
KA
Irizarry
Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC, USA.|Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
James
J
Bain
Departments of Pediatrics, Psychiatry and Behavioral Sciences, Kansas University Medical Center, Kansas City, KS, USA.
Merlin G
MG
Butler
Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Olga
O
Ilkayeva
Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Michael
M
Muehlbauer
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Andrea M
AM
Haqq
Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, NC, USA.|Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Michael
M
Freemark
D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D002648:Child; D005215:Fasting / Q000097:blood; D005260:Female; D054439:Ghrelin / Q000097:blood; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications*; D019894:Peptide YY / Q000097:blood; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
C499918:ADIPOQ protein, human; D052242:Adiponectin; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D019894:Peptide YY; D013006:Growth Hormone