ESPE Abstracts (2018) 89 RFC10.3

ESPE2018 Rapid Free Communications Late Breaking (6 abstracts)

Developmental Regulation of Obestatin and Adropin in Prader-Willi Syndrome and Non-Syndromic Obesity: Associations with Weight, BMI-z, HOMA-IR, and Lipid Profile

Camila E Orsso a , Andrew A Butler b , Michael J Muehlbauer c , Huaxia N Cui c , Daniela A Rubin d , Mohammadreza Pakseresht a , Merlin G Butler e , Carla M Prado a , Michael Freemark f & Andrea M Haqq a,

aDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada; bDepartment of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, Missouri, USA; cSarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina, USA; dDepartment of Kinesiology, California State University, Fullerton, California, USA; eDepartments of Psychiatry, Behavioral Sciences, and Pediatrics, Kansas University Medical Center, Kansas, Kansas, USA; fDepartment of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA; gDepartment of Pediatrics, University of Alberta, Edmonton, Canada

Background: The peptides obestatin and adropin are thought to regulate glucose and lipid metabolism, weight gain, and fluid intake in adults. The roles of obestatin and adropin in the regulation of weight and glucose and lipid metabolism in Prader-Willi syndrome (PWS) and non-syndromic pediatric obesity are poorly understood. This study compares the concentrations of obestatin and adropin in infants and children with PWS and age- and BMI-z matched controls, and explores the associations between these peptides and other energy-regulating hormones.

Methods: The cohort included 21 infants and 14 children with PWS and 31 controls of similar age, sex, and BMI-z-score. Fasting plasma obestatin and adropin were measured by ELISA. Fasting plasma ghrelin, leptin, and insulin were assayed by radioimmunoassay, and lipid panel and glucose by a Hitachi 911 autoanalyzer.

Results: Obestatin (median 2691.0 pg/ml) and adropin (3.50 ng/ml) levels were higher in infants with PWS than controls (obestatin, 2101.0 pg/ml, P=0.04; adropin, 2.57 ng/ml, P=0.05); adropin was also higher in older children with PWS (2.69 vs controls, 1.93 ng/ml, P=0.04). Growth hormone (GH) treatment had no effects on obestatin or adropin in PWS and levels were comparable in insulin resistant and insulin sensitive subjects. The ratio of ghrelin to obestatin declined from infancy to childhood but was higher in older PWS than older controls (P< 0.01 and P<0.0005, respectively). Adropin correlated with fasting glucose in the PWS group only (rS=0.78, P<0.01). Analysis of the lipid profile of children with PWS revealed higher high-density lipoprotein (HDL, 49.10 mg/dl) and lower triglycerides (TG, 55.50 mg/dl) compared to controls (HDL, 32.35 mg/dl, P=0.03; TG, 80.00 mg/dl, P=0.03) but similar low-density lipoprotein (PWS, 78.50 vs controls, 85.95 mg/dl, P=0.86) and total cholesterol (PWS, 132.00 vs controls, 123.50 mg/dl, P=0.86). Obestatin was correlated with HDL (rS=−0.569, P=0.034) and TG (rS=0.541, P=0.046) in older controls only.

Conclusions: Higher levels of obestatin and adropin in PWS may have implications for glucose and lipid metabolism and water intake. Changes in the ratio of ghrelin to obestatin suggest changes in the processing of preproghrelin to ghrelin and obestatin during development and preferential processing of preproghrelin to mature ghrelin in children with PWS.

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