Ilaria Barchetta1, Laura Bertoccini1, Federica Sentinelli2, Diego Bailetti2, Giacomo Marini3, Flavia Agata Cimini1, Valentina Ceccarelli1, Joachim Struck4, Janin Schulte4, Sandro Loche5, Efisio Cossu3, Olle Melander6, Maria G Cavallo1, Marco G Baroni7. 1. Department of Experimental Medicine, Sapienza University of Rome, Italy. 2. Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L'Aquila, Italy; Department of Experimental Medicine, Sapienza University of Rome, Italy. 3. Department of Medical Sciences and Public Health, University of Cagliari, Italy. 4. SphingoTec GmbH, Hennigsdorf, Germany. 5. Pediatric Endocrine Unit, Ospedale Pediatrico Microcitemico "A. Cao", Cagliari, Italy. 6. Department of Clinical Sciences Malmö, Lund University, Malmoe, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden. 7. Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L'Aquila, Italy; Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, Pozzilli, Is, Italy. Electronic address: marcogiorgio.baroni@univaq.it.
Abstract
BACKGROUND AND AIMS: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. METHODS AND RESULTS: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036). CONCLUSIONS: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
BACKGROUND AND AIMS: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. METHODS AND RESULTS: For this longitudinal retrospective study, we studied 151 overweight/obesechildren undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036). CONCLUSIONS: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
Authors: Beatriz Villar; Laia Bertran; Carmen Aguilar; Jessica Binetti; Salomé Martínez; Fàtima Sabench; Monica Real; David Riesco; Marta París; Daniel Del Castillo; Cristóbal Richart; Teresa Auguet Journal: Metabolites Date: 2021-06-10