Plasma angiopoietin-like 4 is related to phospholipid transfer protein activity in diabetic and non-diabetic subjects: role of enhanced low grade inflammation

Eke G Gruppen,Sander Kersten,Robin P F Dullaart

doi:10.1186/s12944-018-0717-5

Abstract

BackgroundAngiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase, whereas phospholipid transfer protein (PLTP) enhances hepatic triglyceride secretion. Both factors may be upregulated by inflammatory pathways. Since the extent to which these circulating factors are interrelated is unknown, we determined the relationship between plasma ANGPTL4 and PLTP activity, and assessed whether such a relationship could be explained by high sensitivity C-reactive protein (hsCRP) levels as a marker of low-grade chronic inflammation.MethodsFasting plasma ANGPTL4, PLTP activity (liposome-vesicle high density lipoprotein system) and hsCRP were measured in 41 type 2 diabetic (T2DM) subjects and 36 non-diabetic subjects.ResultsPlasma ANGPTL4 and PLTP activity were increased in T2DM (p < 0.001 for each), coinciding with elevated hsCRP, triglycerides and non-esterified fatty acids (NEFA) (p = 0.031 to 0.001). In univariate analysis, ANGTLP4 was correlated with PLTP activity (Rs = 0.309, p = 0.006), whereas both factors were related to hsCRP and NEFA levels (Rs = 0.304 to 0.411, p < 0.01 to < 0.001). In multivariable linear regression analysis adjusting for age, sex, glucose, total cholesterol, triglycerides and NEFA, ANGPTL4 and PLTP activity each remained positively associated with hsCRP (β = 0.315, p = 0.003 and β = 0.299, p = 0.034, respectively). Plasma ANGPTL4 remained positively associated with PLTP activity when taking account of age, sex, glucose, total cholesterol, triglycerides and NEFA (β = 0.315, p = 0.003). Notably, this association disappeared after further adjustment for hsCRP (β = 0.131, p = 0.25).ConclusionsIn conclusion, plasma ANGPTL4 and PLTP activity are interrelated, which may at least in part be explained by low-grade chronic inflammation. A pro-inflammatory state could affect triglyceride metabolism via concerted effects on ANGPTL4 and PLTP.

Highlights

Angiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase, whereas phospholipid transfer protein (PLTP) enhances hepatic triglyceride secretion
The metabolism of triglycerides is governed by phospholipid transfer protein (PLTP), a lipid transfer protein that is produced by a variety of cell systems, including hepatocytes, adipocytes and macrophages [11,12,13]
Studies in transgenic mice have shown that PLTP deficiency attenuates the secretion of very low density lipoproteins (VLDL) by the liver, whereas PLTP overexpression has the opposite effect [14, 15]

Summary

Introduction

Angiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase, whereas phospholipid transfer protein (PLTP) enhances hepatic triglyceride secretion. Both factors may be upregulated by inflammatory pathways. During the past few years, the key role of angiopoietin like proteins (ANGPTL) in lipid metabolism and energy balance is increasingly appreciated [1,2,3]. Among this family of proteins, ANGPTL4 is a secreted glycoprotein that is highly expressed in liver and adipose tissue [1,2,3]. Studies in humans have shown that plasma PLTP activity is increased after a prolonged exposure to an intravenously administered triglyceride emulsion, while a decrease has been observed when plasma NEFA availability is attenuated by Acipimox administration [16, 17]

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Conclusion