Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: Sex differences and the role of growth hormone

Abstract

© 2015 John Wiley & Sons Ltd.Objectives 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.

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Published Version (Please cite this version)

10.1111/cen.12766

Publication Info

Irizarry, Krystal A, James Bain, Merlin G Butler, Olga Ilkayeva, Michael Muehlbauer, Andrea M Haqq and Michael Freemark (2015). Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: Sex differences and the role of growth hormone. Clinical Endocrinology, 83(6). pp. 797–805. 10.1111/cen.12766 Retrieved from https://hdl.handle.net/10161/11607.

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Scholars@Duke

Bain

James R. Bain

Professor in Medicine
Ilkayeva

Olga Ilkayeva

Assistant Professor in Medicine

Olga Ilkayeva, Ph.D., is the Director of the Metabolomics Core Laboratory at Duke Molecular Physiology Institute. She received her Ph.D. training in Cell Regulation from UT Southwestern Medical Center at Dallas, TX. Her postdoctoral research in the laboratory of Dr. Chris Newgard at Duke University Medical Center focused on lipid metabolism and regulation of insulin secretion. As a research scientist at the Stedman Nutrition and Metabolism Center, Dr. Ilkayeva expanded her studies to include the development of targeted mass spectrometry analyses. Currently, she works on developing and validating quantitative mass spectrometry methods used for metabolic profiling of various biological models with emphasis on diabetes, obesity, cardiovascular disease, and the role of gut microbiome in both health and disease.

Freemark

Michael Scott Freemark

Robert C. Atkins, M.D. and Veronica Atkins Distinguished Professor of Pediatrics, in the School of Medicine

The primary objective of my basic research has been to elucidate the roles of placental and fetal hormones in the regulation of maternal metabolism and fetal growth. My work has focused on the lactogenic hormones produced by the pituitary gland and placenta. To that end we used targeted knockout mice to explore the molecular mechanisms by which prolactin and placental lactogen regulate pancreatic beta cell mass and insulin production during pregnancy and postnatal life.

I also have a longstanding clinical research interest in the pathogenesis and treatment of obesity and hyperlipidemia and the prevention of type 2 diabetes. In previous studies we showed that the drug metformin reduces fat stores and blood glucose and insulin levels in obese adolescents and may reduce the risk of progression to diabetes in selected patients. We have also examined the unique metabolic characteristics of Prader Willi syndrome, a genetic obesity disorder.

Finally, my colleagues and I have performed detailed studies of hormone production and intermediary metabolism in malnourished children in Uganda, Bangladesh, Liberia, and Burkina Faso and characterized the effects of concurrent HIV infection on nutritional recovery.  We showed that the adipocyte hormone leptin is a major determinant of morbidity and mortality in children with moderate and severe acute malnutrition. 


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