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. 2023 Mar 30;24(7):6460.
doi: 10.3390/ijms24076460.

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

Federica Sentinelli  1   2 , Ilaria Barchetta  2 , Flavia Agata Cimini  2 , Sara Dule  2 , Diego Bailetti  1   2 , Efisio Cossu  3 , Arcangelo Barbonetti  1 , Maria Totaro  1 , Olle Melander  4   5 , Maria Gisella Cavallo  2 , Marco Giorgio Baroni  1   6
Affiliations

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

Federica Sentinelli et al. Int J Mol Sci. .

Abstract

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.

Keywords: blood lipids; children; gastrointestinal peptides; gene; insulin resistance; neurotensin; obesity; single nucleotide polymorphism.

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Conflict of interest statement

The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Neurotensin gene (NTS) identified polymorphisms.
See this image and copyright information in PMC

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