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Metabolism
Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes
  1. Nathanja Tjeerdema1,
  2. Anastasia Georgiadi2,
  3. Jacqueline T Jonker1,
  4. Marjolijn van Glabbeek1,
  5. Reza Alizadeh Dehnavi1,
  6. Jouke T Tamsma1,
  7. Johannes W A Smit1,3,
  8. Sander Kersten2,
  9. Patrick C N Rensen1,4
  1. 1Departments of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Nutrition, Metabolism and Genomics group, Wageningen University, Wageningen, The Netherlands
  3. 3Department of Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands
  4. 4Department of Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Nathanja Tjeerdema; N.Tjeerdema{at}lumc.nl

Abstract

Background Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages.

Objective To assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).

Design We studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS−I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro.

Results As compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS−I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS−I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages.

Conclusions Plasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli.

  • Inflammatory Process in Diabetes
  • Metabolic Syndrome

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjdrc-2014-000034

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