ANGPTL-4 is Associated with Obesity and Lipid Profile in Children and Adolescents.

Silvia Barja-Fernández,Verónica Pena-León,Ángel Gil,Gloria Bueno,Concepción M Aguilera,Mercedes Gil-Campos,Felipe F Casanueva,Luis A Moreno,Rubén Nogueiras,Manuel Ruiz-Piñon,Cintia Folgueira,Carlos Diéguez,Rosaura Leis,Rocío Vázquez-Cobela,Patricia González-Saenz,María García-Palacios,Cecilia Castelao,Luisa M Seoane

doi:10.3390/nu11061340

Abstract

Angiopoietin-like protein 4 (ANGPTL-4) regulates lipidic metabolism and affects energy homeostasis. However, its function in children with obesity remains unknown. We investigated plasma ANGPTL-4 levels in children and its relationship with body mass index (BMI) and different lipidic parameters such as free fatty acids (FFA). Plasma ANGPTL-4 levels were analyzed in two different cohorts. In the first cohort (n = 150, age 3–17 years), which included children with normal weight or obesity, we performed a cross-sectional study. In the second cohort, which included only children with obesity (n = 20, age 5–18 years) followed up for two years after an intervention for weight loss, in which we performed a longitudinal study measuring ANGPTL-4 before and after BMI-loss. In the cross-sectional study, circulating ANGPTL-4 levels were lower in children with obesity than in those with normal weight. Moreover, ANGPTL-4 presented a negative correlation with BMI, waist circumference, weight, insulin, homeostasis model assessment of insulin resistance index (HOMA index), triglycerides, and leptin, and a positive correlation with FFA and vitamin-D. In the longitudinal study, the percent change in plasma ANGPTL-4 was correlated with the percent change in FFA, total-cholesterol and high-density lipoprotein cholesterol. This study reveals a significant association of ANGPTL-4 with pediatric obesity and plasma lipid profile.

Highlights

Angiopoietin-like protein 4 (ANGPTL-4) is mainly produced in adipose tissue and liver [1,2], and, by a broad range of tissues [3,4,5]
When the population was classified by sexual development, both children and adolescents with obesity showed higher body weight, height, body mass index (BMI), waist circumference, HOMA index, and plasma insulin, and leptin than those with normal weight
Only pre-pubertal children with obesity exhibited a diminution of glucose concentration with respect to those with a normal weight that was not found in adolescent subjects

Summary

Introduction

Angiopoietin-like protein 4 (ANGPTL-4) is mainly produced in adipose tissue and liver [1,2], and, by a broad range of tissues [3,4,5]. ANGPTL-4 gene codes for a native full-length glycoprotein (~45–65 kDa), which is secreted and processed by proprotein convertases releasing the N-terminal and the monomeric C-terminal fragments [7,8]. The complete form is mostly released from the adipose tissue while the N-terminal portion is primarily produced in the liver [9]. Both ANGPTL-4 truncated forms and full-length protein are present in the bloodstream [9,10]. Several studies indicate that only the full-length and N-terminal portion inhibit LPL, whereas the C-terminal fragment participates in others functions, such as angiogenesis and protection of cancer cells against apoptosis and anoikis [11,12]

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