Novel Proteome Targets Marking Insulin Resistance in Metabolic Syndrome

Overview

Journal Nutrients

Date 2024 Jun 27

PMID 38931177

Authors

Moritz V Warmbrunn

Harsh Bahrar

Nicolien C de Clercq

Annefleur M Koopen

Pieter F de Groot

Joost Rutten

Leo A B Joosten

Ruud S Kootte

Kristien E C Bouter

Kasper W Ter Horst

Annick V Hartstra

Mireille J Serlie

Maarten R Soeters

Daniel H van Raalte

Mark Davids

Evgeni Levin

Hilde Herrema

Niels P Riksen

Mihai G Netea

Albert K Groen

Max Nieuwdorp

Affiliations

Soon will be listed here.

Abstract

Context/objective: In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers.

Design/methods: In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd). Machine learning models and conventional statistics were used to identify biomarkers of insulin resistance. Findings were replicated in a cohort with n = 282 obese men and women with (n = 156) and without (n = 126) MetSyn. In addition to this, the relation between biomarkers and adipose tissue was assessed by nuclear magnetic resonance imaging.

Results: Peripheral insulin resistance is marked by changes in proteins related to inflammatory processes such as IL-1 and TNF-receptor and superfamily members. These proteins can distinguish between insulin-resistant and insulin-sensitive individuals (AUC = 0.72 ± 0.10) with MetSyn. These proteins were also associated with IFG, liver fat (rho 0.36, = 1.79 × 10) and visceral adipose tissue (rho = 0.35, = 6.80 × 10). Interestingly, these proteins had the strongest association in the MetSyn subgroup compared to individuals without MetSyn.

Conclusions: MetSyn associated with insulin resistance is characterized by protein changes related to body fat content, insulin signaling and pro-inflammatory processes. These findings provide novel targets for intervention studies and should be the focus of future in vitro and in vivo studies.

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