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Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children

Neurotensin (NT) is a small protein implicated in the regulation of energy balance which acts as both a neurotransmitter in the central nervous system and as a gastrointestinal peptide. In the gut, NT is secreted after fat ingestion and promotes the absorption of fatty acids. The circulating levels...

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Autores principales: Sentinelli, Federica, Barchetta, Ilaria, Cimini, Flavia Agata, Dule, Sara, Bailetti, Diego, Cossu, Efisio, Barbonetti, Arcangelo, Totaro, Maria, Melander, Olle, Cavallo, Maria Gisella, Baroni, Marco Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095103/
https://www.ncbi.nlm.nih.gov/pubmed/37047432
http://dx.doi.org/10.3390/ijms24076460
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author Sentinelli, Federica
Barchetta, Ilaria
Cimini, Flavia Agata
Dule, Sara
Bailetti, Diego
Cossu, Efisio
Barbonetti, Arcangelo
Totaro, Maria
Melander, Olle
Cavallo, Maria Gisella
Baroni, Marco Giorgio
author_facet Sentinelli, Federica
Barchetta, Ilaria
Cimini, Flavia Agata
Dule, Sara
Bailetti, Diego
Cossu, Efisio
Barbonetti, Arcangelo
Totaro, Maria
Melander, Olle
Cavallo, Maria Gisella
Baroni, Marco Giorgio
author_sort Sentinelli, Federica
collection PubMed
description Neurotensin (NT) is a small protein implicated in the regulation of energy balance which acts as both a neurotransmitter in the central nervous system and as a gastrointestinal peptide. In the gut, NT is secreted after fat ingestion and promotes the absorption of fatty acids. The circulating levels of its precursor, pro-NT, predicts the presence and development of metabolic and cardiovascular diseases. Despite the extensive knowledge on the dynamic changes that occur to pro-NT = after fat load, the determinants of fasting pro-NT are unknown. The aim of this study was to determine the possible genetic regulation of plasma pro-NT. The NT gene (NTS) was sequenced for potential functional variants, evaluating its entire genomic and potentially regulatory regions, in DNA from 28 individuals, stratified by low and high pro-NT levels. The identified variant differently distributed in the two pro-NT subgroups was genotyped in a cohort of nine hundred and thirty-two overweight/obese children and adolescents. A total of seven sequence variations across the NTS gene, none of them located in coding regions, were identified. The rs2234762 polymorphism, sited in the NTS gene promoter, was statistically more frequent in the lowest pro-NTS level group. Carriers of the rs2234762 variant showed lower pro-NT levels, after adjusting for sex, age, BMI, triglycerides and the Tanner stage. Having NTS rs2234762 predicted less pronounced insulin resistance at the 6.5-year follow-up with OR: 0.46 (0.216–0.983), at the logistic regression analysis adjusted for age, sex and BMI. In conclusion, the NTS rs2234762 gene variant is a determinant of reduced circulating pro-NT levels in overweight and obese children, which predisposes this group to a more favorable metabolic profile and a reduced insulin resistance later in life, independently from metabolic confounders.
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spelling pubmed-100951032023-04-13 Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children Sentinelli, Federica Barchetta, Ilaria Cimini, Flavia Agata Dule, Sara Bailetti, Diego Cossu, Efisio Barbonetti, Arcangelo Totaro, Maria Melander, Olle Cavallo, Maria Gisella Baroni, Marco Giorgio Int J Mol Sci Article Neurotensin (NT) is a small protein implicated in the regulation of energy balance which acts as both a neurotransmitter in the central nervous system and as a gastrointestinal peptide. In the gut, NT is secreted after fat ingestion and promotes the absorption of fatty acids. The circulating levels of its precursor, pro-NT, predicts the presence and development of metabolic and cardiovascular diseases. Despite the extensive knowledge on the dynamic changes that occur to pro-NT = after fat load, the determinants of fasting pro-NT are unknown. The aim of this study was to determine the possible genetic regulation of plasma pro-NT. The NT gene (NTS) was sequenced for potential functional variants, evaluating its entire genomic and potentially regulatory regions, in DNA from 28 individuals, stratified by low and high pro-NT levels. The identified variant differently distributed in the two pro-NT subgroups was genotyped in a cohort of nine hundred and thirty-two overweight/obese children and adolescents. A total of seven sequence variations across the NTS gene, none of them located in coding regions, were identified. The rs2234762 polymorphism, sited in the NTS gene promoter, was statistically more frequent in the lowest pro-NTS level group. Carriers of the rs2234762 variant showed lower pro-NT levels, after adjusting for sex, age, BMI, triglycerides and the Tanner stage. Having NTS rs2234762 predicted less pronounced insulin resistance at the 6.5-year follow-up with OR: 0.46 (0.216–0.983), at the logistic regression analysis adjusted for age, sex and BMI. In conclusion, the NTS rs2234762 gene variant is a determinant of reduced circulating pro-NT levels in overweight and obese children, which predisposes this group to a more favorable metabolic profile and a reduced insulin resistance later in life, independently from metabolic confounders. MDPI 2023-03-30 /pmc/articles/PMC10095103/ /pubmed/37047432 http://dx.doi.org/10.3390/ijms24076460 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sentinelli, Federica
Barchetta, Ilaria
Cimini, Flavia Agata
Dule, Sara
Bailetti, Diego
Cossu, Efisio
Barbonetti, Arcangelo
Totaro, Maria
Melander, Olle
Cavallo, Maria Gisella
Baroni, Marco Giorgio
Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
title Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
title_full Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
title_fullStr Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
title_full_unstemmed Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
title_short Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
title_sort neurotensin gene rs2234762 c>g variant associates with reduced circulating pro-nt levels and predicts lower insulin resistance in overweight/obese children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095103/
https://www.ncbi.nlm.nih.gov/pubmed/37047432
http://dx.doi.org/10.3390/ijms24076460
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