Leukotriene production is increased in abdominal obesity.

Magnus Bäck,Elodie Leprieur,Vincent Attalin,Catherine Boegner,Antoine Avignon,Ariane Sultan,Françoise Stanke-Labesque,Cedric Moro

doi:10.1371/journal.pone.0104593

Abstract

Obesity is a major risk factor for insulin resistance and type-2 diabetes. A chronic low grade inflammatory state has been described during obesity and associated with insulin resistance pathogenesis. Results from animal studies are in favor of a role of the leukotriene (LT) pathway in obesity induced-insulin resistance. However, there is a paucity of data regarding this association in human obesity. Therefore, the aim of this study was to investigate whether LT production was associated with insulin resistance and other metabolic parameters in a cohort of obese subjects. Forty-six (70% females) obese subjects (BMI≧30 kg/m2) without known diabetes and without inflammatory disease (CRP<10 mg/l) were included. Median age was 44 years (16–80) with a median BMI of 36.8 kg/m2 (30–51). Insulin resistance was evaluated by HOMA-IR index and glucose tolerance test. Urinary LTE4 (U-LTE4) concentration was measured by enzyme immune assay. Screening for obstructive sleep apnea was performed. There was a positive association of U-LTE4 with waist to hip ratio, systolic blood pressure and HOMA-IR in univariate analysis. Further, waist to hip ratio remained the only parameter significantly correlated with U-LTE4, in adjusted multivariate analysis. Taken together, these results confirm the previously established notion of chronic low grade inflammation in obesity and further suggests a role for the LT pathway in obesity-associated development of insulin resistance in humans.

Highlights

Obesity is a major risk factor for insulin resistance and type-2 diabetes
Whereas the levels of Urinary LTE4 (U-LTE4) did not differ in groups with and without hypertension, and not between high and low HDL and TG, U-LTE4 was significantly higher in subjects with a high waist to hip ratio and in subjects with high fasting plasma glucose (Fig. 1)
The association of U-LTE4 with metabolic parameters in the present cohort of obese subjects provides support to the notion that adipose tissue may serve as a source of inflammatory mediators interfering with insulin sensitivity

Summary

Introduction

Obesity is a major risk factor for insulin resistance and type-2 diabetes. A wealth of evidence indicates that these metabolic comorbidities are associated withPLOS ONE | DOI:10.1371/journal.pone.0104593 December 1, 2014Leukotrienes, Abdominal Obesity presence of low-grade chronic inflammation. Adipose tissue overexpression of selected members of the 5-lipoxygenase pathway and increased LT production have been recently described in animal models [3, 6], including obese rodents [3, 6, 7]. In these conditions, 5-lipoxygenase products exert potent proinflammatory actions, such as induction of nuclear factor (NF)kB [8] and secretion of proinflammatory and insulin resistant adipokines (i.e., monocyte chemotactic protein-1, tumor necrosis factor-a, macrophage inflammatory protein-1, and interleukin-6) that could potentially contribute to systemic insulin resistance. There is a paucity of information on the association of the LT pathway with insulin resistance derived from human studies

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