Neurotensin accelerates atherosclerosis and increases circulating levels of short-chain and saturated triglycerides.

Heart disease High-fat diet Neurotensin Obesity Small intestine

Journal

Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543

Informations de publication

Date de publication:
15 Feb 2024
Historique:
received: 17 11 2023
revised: 25 01 2024
accepted: 07 02 2024
medline: 1 3 2024
pubmed: 1 3 2024
entrez: 29 2 2024
Statut: aheadofprint

Résumé

Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown. Nt Atherosclerotic plaque formation is attenuated in Nt-deficient mice through mechanisms that are independent of reductions in circulating cholesterol and triglycerides but associated with remodeling of the plasma triglyceride pool. An increasing plasma concentration of pro-NT predicts atherosclerotic events in coronary and cerebral arteries independent of all major traditional risk factors, indicating a strong link between NT and atherosclerosis. This plasma lipid profile analysis confirms the association of pro-NT with remodeling of the plasma triglyceride pool in atherosclerotic events. Our findings are the first to directly link NT to increased atherosclerosis and indicate the potential role for NT in preventive and therapeutic strategies for CVD.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown.
METHODS METHODS
Nt
RESULTS RESULTS
Atherosclerotic plaque formation is attenuated in Nt-deficient mice through mechanisms that are independent of reductions in circulating cholesterol and triglycerides but associated with remodeling of the plasma triglyceride pool. An increasing plasma concentration of pro-NT predicts atherosclerotic events in coronary and cerebral arteries independent of all major traditional risk factors, indicating a strong link between NT and atherosclerosis. This plasma lipid profile analysis confirms the association of pro-NT with remodeling of the plasma triglyceride pool in atherosclerotic events.
CONCLUSIONS CONCLUSIONS
Our findings are the first to directly link NT to increased atherosclerosis and indicate the potential role for NT in preventive and therapeutic strategies for CVD.

Identifiants

pubmed: 38423808
pii: S0021-9150(24)00039-X
doi: 10.1016/j.atherosclerosis.2024.117479
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

117479

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Jing Li (J)

University of Kentucky, Lexington, KY, 40536, USA.

Liping Yang (L)

University of Kentucky, Lexington, KY, 40536, USA.

Jun Song (J)

University of Kentucky, Lexington, KY, 40536, USA.

Baoxiang Yan (B)

University of Kentucky, Lexington, KY, 40536, USA.

Andrew J Morris (AJ)

University of Arkansas for Medical Sciences, Little Rock, AR, 77205, USA.

Hunter Moseley (H)

University of Kentucky, Lexington, KY, 40536, USA.

Robert Flight (R)

University of Kentucky, Lexington, KY, 40536, USA.

Chi Wang (C)

University of Kentucky, Lexington, KY, 40536, USA.

Jinpeng Liu (J)

University of Kentucky, Lexington, KY, 40536, USA.

Heidi L Weiss (HL)

University of Kentucky, Lexington, KY, 40536, USA.

Edward F Morris (EF)

Washington University in St. Louis, St. Louis, Missouri, 63110, USA.

Ilyes Abdelhamid (I)

Lipotype, 01307, Dresden, Germany.

Mathias J Gerl (MJ)

Lipotype, 01307, Dresden, Germany.

Olle Melander (O)

Lund University, Malmo, 221 00, Lund, Sweden. Electronic address: Olle.Melander@med.lu.se.

Susan Smyth (S)

University of Arkansas for Medical Sciences, Little Rock, AR, 77205, USA.

B Mark Evers (BM)

University of Kentucky, Lexington, KY, 40536, USA. Electronic address: Mark.Evers@uky.edu.

Classifications MeSH