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

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Background: Angiopoietin-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. Methods: Fasting 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. Results: Plasma 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). Conclusions: In 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.
LanguageEnglish
Article number60
JournalLipids in Health and Disease
Volume17
DOIs
Publication statusPublished - 27 Mar 2018

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Angiopoietins
Phospholipid Transfer Proteins
Inflammation
Plasmas
C-Reactive Protein
Triglycerides
Fatty Acids
Cholesterol
angiopoietin 4
Glucose
Lipoprotein Lipase
HDL Lipoproteins
Linear regression
Metabolism
Regression analysis
Liposomes
Linear Models
Fasting
Regression Analysis

Keywords

  • Angiopoietin-like4
  • High sensitivity C-reactive protein
  • Non-esterified fatty acids
  • Phospholipid transfer protein activity
  • Type 2 diabetes mellitus

Cite this

@article{5ec8e6a854b84ca089652978b6563b7c,
title = "Plasma angiopoietin-like 4 is related to phospholipid transfer protein activity in diabetic and non-diabetic subjects: Role of enhanced low grade inflammation",
abstract = "Background: Angiopoietin-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. Methods: Fasting 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. Results: Plasma 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). Conclusions: In 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.",
keywords = "Angiopoietin-like4, High sensitivity C-reactive protein, Non-esterified fatty acids, Phospholipid transfer protein activity, Type 2 diabetes mellitus",
author = "Gruppen, {Eke G.} and Sander Kersten and Dullaart, {Robin P.F.}",
year = "2018",
month = "3",
day = "27",
doi = "10.1186/s12944-018-0717-5",
language = "English",
volume = "17",
journal = "Lipids in Health and Disease",
issn = "1476-511X",
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}

Plasma angiopoietin-like 4 is related to phospholipid transfer protein activity in diabetic and non-diabetic subjects : Role of enhanced low grade inflammation. / Gruppen, Eke G.; Kersten, Sander; Dullaart, Robin P.F.

In: Lipids in Health and Disease, Vol. 17, 60, 27.03.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Plasma angiopoietin-like 4 is related to phospholipid transfer protein activity in diabetic and non-diabetic subjects

T2 - Lipids in Health and Disease

AU - Gruppen, Eke G.

AU - Kersten, Sander

AU - Dullaart, Robin P.F.

PY - 2018/3/27

Y1 - 2018/3/27

N2 - Background: Angiopoietin-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. Methods: Fasting 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. Results: Plasma 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). Conclusions: In 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.

AB - Background: Angiopoietin-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. Methods: Fasting 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. Results: Plasma 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). Conclusions: In 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.

KW - Angiopoietin-like4

KW - High sensitivity C-reactive protein

KW - Non-esterified fatty acids

KW - Phospholipid transfer protein activity

KW - Type 2 diabetes mellitus

U2 - 10.1186/s12944-018-0717-5

DO - 10.1186/s12944-018-0717-5

M3 - Article

VL - 17

JO - Lipids in Health and Disease

JF - Lipids in Health and Disease

SN - 1476-511X

M1 - 60

ER -