Identification of Anti-Long Chain Saturated Fatty Acid IgG Antibodies in Serum of Patients with Type 2 Diabetes.

Dequina A Nicholas,Carlos A Casiano,Marco Larios,Ava M Boston,William H R Langridge,Zaida Cordero-Macintyre,Anthony F Firek,Nan Sun Kim,Lorena M Salto,W Lawrence Beeson,Marino De Leon

doi:10.1155/2015/196297

Abstract

High levels of serum long chain saturated fatty acids (LCSFAs) have been associated with inflammation in type 2 diabetes. Dietary SFAs can promote inflammation, the secretion of IgG antibodies, and secretion of the proinflammatory cytokine IL-1β. This study characterizes anti-LCSFA IgG antibodies from patients with type 2 diabetes. Serum samples from several cohorts with type 2 diabetes were analyzed for the presence of anti-LCSFA IgG, the cytokine IL-1β, and nonesterified fatty acids. Anti-LCSFA IgG was isolated from patient samples and used for in vitro characterization of avidity and specificity. A cohort participating in En Balance, a diabetes health education program that improved diabetes management, tested positive for anti-LCSFA IgG. Following the 3-month program, the cohort showed a significant reduction in anti-LCSFA IgG levels. Anti-LCSFA antibodies isolated from these patients demonstrated high avidity, were specific for long chain SFAs, and correlated with serum fatty acids in patients with managed type 2 diabetes. Interestingly, anti-LCSFA IgG neutralized PA-induced IL-1β secretion by dendritic cells. Our data shows that nonesterified SFAs are recognized by IgG antibodies present in human blood. The identification of anti-LCSFA IgG antibodies in human sera establishes a basis for further exploration of lipid induced immune responses in diabetic patients.

Highlights

Growing evidence in the literature supports the role of increased dietary intake of saturated fats in the initiation of inflammation [1, 2]
We found that 100% (36/36) of the Hispanics with type 2 diabetes tested positive for anti-long chain saturated fatty acids (LCSFAs) IgG antibodies before undergoing the diabetes education program (Figure 5(a))
We found that preabsorption of palmitic acid (PA) with IgG antibodies from patients with high levels of anti-LCSFA IgG significantly reduced dendritic cells (DCs) secretion of IL-1β (Figure 6(c))

Summary

Introduction

Growing evidence in the literature supports the role of increased dietary intake of saturated fats in the initiation of inflammation [1, 2]. Elevated plasma levels of nonesterified FAs have been extensively correlated to insulin resistance, the role of specific FAs, such as palmitic acid (PA), is not well understood [3, 4]. Obesity is closely associated with increased levels of proinflammatory cytokines [5]. Visceral adipose tissue is a major site of obesity-induced inflammation, and dyslipidemia is a major factor in the recruitment of activated immune cells such as macrophages, T cells, NK cells, dendritic cells, and B cells to visceral adipose tissue. Infiltrating adipose immune cells are a major source of Mediators of Inflammation proinflammatory cytokines in obesity-induced inflammation and type 2 diabetes [5,6,7]. The proinflammatory cytokine IL-1β can directly cause insulin resistance in insulinsensitive cells [5, 8,9,10,11]. PA has been shown to activate Toll-like receptor 4 on immune cells and induce secretion of IL-1β [12]

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