Calprotectin — A Novel Marker of Obesity

Ole Hartvig Mortensen,Anders Rinnov Nielsen,Anne Marie Petersen,Christian Erikstrup,Christian Philip Fischer,Rikke Krogh-Madsen,Peter Plomgaard,Sarah Taudorf,Bente Klarlund Pedersen,Birgitte Lindegaard,Adrian Vella

doi:10.1371/journal.pone.0007419

Abstract

BackgroundThe two inflammatory molecules, S100A8 and S100A9, form a heterodimer, calprotectin. Plasma calprotectin levels are elevated in various inflammatory disorders. We hypothesized that plasma calprotectin levels would be increased in subjects with low-grade systemic inflammation i.e. either obese subjects or subjects with type 2 diabetes.Methodology/Principal FindingsPlasma calprotectin and skeletal muscle S100A8 mRNA levels were measured in a cohort consisting of 199 subjects divided into four groups depending on presence or absence of type 2 diabetes (T2D), and presence or absence of obesity. There was a significant interaction between obesity and T2D (p = 0.012). Plasma calprotectin was increased in obese relative to non-obese controls (p<0.0001), whereas it did not differ between obese and non-obese patients with T2D (p = 0.62). S100A8 mRNA levels in skeletal muscle were not influenced by obesity or T2D. Multivariate regression analysis (adjusting for age, sex, smoking and HOMA2-IR) showed plasma calprotectin to be strongly associated with BMI, even when further adjusted for fitness, CRP, TNF-α or neutrophil number.Conclusions/SignificancePlasma calprotectin is a marker of obesity in individuals without type 2 diabetes.

Highlights

Two novel inflammatory molecules belonging to the S100 protein family have been described, S100A8 (MRP8) and S100A9 (MRP14)[1]
As low-grade systemic inflammation is a hallmark of both obesity and type 2 diabetes (T2D) we studied the levels of plasma calprotectin and S100A8 skeletal muscle mRNA levels using a cross-sectional case control design in which patients with T2D and healthy controls were closely matched, according to age and sex and according to body mass index (BMI)
Plasma calprotectin was positively associated with BMI (Fig. 1C), waist-hip-ratio (WHR), total fat mass, fasting insulin, HOMA2-IR, triglyceride, neutrophils and CRP, and negatively associated with HDL, LDL, IL-6, TNFa, and there was a trend for VO2max

Summary

Introduction

Two novel inflammatory molecules belonging to the S100 protein family have been described, S100A8 (MRP8) and S100A9 (MRP14)[1]. S100A8 and S100A9 form monovalent homodimers and a heterodimer, known as calprotectin, in a calcium-dependent manner. Both proteins are predominantly expressed in myeloid cells depending on the stage of cell differentiation and inflammatory status[1], they have been found to be expressed in skeletal muscle[2]. Phagocytes expressing S100A8 and S100A9 and elevated plasma calprotectin levels are found in a variety of chronic inflammatory conditions, including rheumatoid arthritis, allograft rejections, and inflammatory bowel and lung diseases[4]. Calprotectin has been found to be increased in plasma following exercise[5] and was recently shown to be released from skeletal muscle tissue [6]. We hypothesized that plasma calprotectin levels would be increased in subjects with low-grade systemic inflammation i.e. either obese subjects or subjects with type 2 diabetes

Methods

Results

Conclusion