Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome

C Mele,A Convertino,G Grugni,P Di Paolo,M Scacchi,D Fintini,P Marzullo,G Aimaretti,S Mai,A Crinò,S Bocchini

doi:10.1007/s40618-020-01444-w

Abstract

PurposeAngiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader–Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown.MethodsThis cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0–17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM).ResultsAt the set level of significance, PWS children showed lower values of FFM (p < 0.01) but healthier insulin profiles (p < 0.01) and PMI values (p < 0.05) than matched controls. By US, the prevalence of NAFLD was similar between groups but less severe in PWS than controls. Analysis of ANGPTL8 levels showed no difference between groups, yet only in PWS ANGPTL8 levels were associated with ALT levels, FLI values and NAFLD. In stepwise multivariable regression analysis on merged data, ANGPTL8 levels were independently predicted by BMI SDS, leptin levels and NAFLD.ConclusionANGPTL8 levels are similar in PWS and controls and, overall, they are directly associated with the presence and severity of NAFLD in patients with PWS.

Highlights

Prader-Willi syndrome (PWS) represents one of the most common form of genetic obesity with an estimated incidence rate of 1 in 25,000 live births [1, 2]
The present study analysed the association between Angiopoietin-like 8 (ANGPTL8) levels and adiposity, metabolic profile and non-alcoholic fatty liver disease (NAFLD) in relation to PWS status in children and adolescents
Our results show that ANGPTL8 levels are comparable between patients with PWS and controls and that, in PWS, this liver-derived protein is closely associated with the presence and severity of NAFLD

Summary

Introduction

Prader-Willi syndrome (PWS) represents one of the most common form of genetic obesity with an estimated incidence rate of 1 in 25,000 live births [1, 2]. It is an imprinted neurobehavioral condition caused by the lack of expression of genes located on the paternal chromosome 15q11.2-q13. Changes in body composition in patients with PWS develop even before hyperphagia occurs [7] and result in higher fat mass (FM) and predominant accumulation of subcutaneous fat, lower fat-free mass (FFM) and greater ratio of intramuscular adipose tissue/skeletal muscle [8], impaired muscle function [9] and decreased excitability of cortical motor areas [10] when compared to controls. In terms of energy homeostasis, the voluntary activity is decreased in PWS and is associated with low values of resting energy expenditure (REE), this defect seems proportional to lower values of lean body mass [11]

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Conclusion