Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: Multicenter tracer kinetic study

J. Borén, G.F. Watts, M. Adiels, S. Söderlund, D.C. Chan, A. Hakkarainen, N. Lundbom, N. Matikainen, J. Kahri, B. Vergès, Hugh Barrett, M.R. Taskinen

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Abstract

© 2015 American Heart Association, Inc. Objectives-Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. Approach and Results-A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, P>0.01; r=0.45, P>0.01) and fractional catabolism (r=0.49, P>0.001; r=0.55, P>0.001) of VLDL1-triglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, P>0.001) and VLDL1-apoB (r=0.53, P>0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL1-triglycerides (r=0.48, P>0.001) and VLDL1-apoB (r=0.51, P>0.001). Conclusions-Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity.
Original languageEnglish
Pages (from-to)2218-2224
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume35
Issue number10
Early online date27 Aug 2015
DOIs
Publication statusPublished - Oct 2015

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Abdominal Obesity
LDL Lipoproteins
Triglycerides
VLDL Lipoproteins
Apolipoproteins B
Apolipoprotein C-III
Fats
Dyslipidemias
Liver
Obesity
Leucine
Isotopes
Glycerol
Lipoproteins
Multicenter Studies
Diabetes Mellitus
Cardiovascular Diseases
very low density lipoprotein triglyceride

Cite this

Borén, J. ; Watts, G.F. ; Adiels, M. ; Söderlund, S. ; Chan, D.C. ; Hakkarainen, A. ; Lundbom, N. ; Matikainen, N. ; Kahri, J. ; Vergès, B. ; Barrett, Hugh ; Taskinen, M.R. / Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: Multicenter tracer kinetic study. In: Arteriosclerosis, thrombosis, and vascular biology. 2015 ; Vol. 35, No. 10. pp. 2218-2224.
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abstract = "{\circledC} 2015 American Heart Association, Inc. Objectives-Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. Approach and Results-A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, P>0.01; r=0.45, P>0.01) and fractional catabolism (r=0.49, P>0.001; r=0.55, P>0.001) of VLDL1-triglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, P>0.001) and VLDL1-apoB (r=0.53, P>0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL1-triglycerides (r=0.48, P>0.001) and VLDL1-apoB (r=0.51, P>0.001). Conclusions-Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity.",
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Borén, J, Watts, GF, Adiels, M, Söderlund, S, Chan, DC, Hakkarainen, A, Lundbom, N, Matikainen, N, Kahri, J, Vergès, B, Barrett, H & Taskinen, MR 2015, 'Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: Multicenter tracer kinetic study' Arteriosclerosis, thrombosis, and vascular biology, vol. 35, no. 10, pp. 2218-2224. https://doi.org/10.1161/ATVBAHA.115.305614

Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: Multicenter tracer kinetic study. / Borén, J.; Watts, G.F.; Adiels, M.; Söderlund, S.; Chan, D.C.; Hakkarainen, A.; Lundbom, N.; Matikainen, N.; Kahri, J.; Vergès, B.; Barrett, Hugh; Taskinen, M.R.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 35, No. 10, 10.2015, p. 2218-2224.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: Multicenter tracer kinetic study

AU - Borén, J.

AU - Watts, G.F.

AU - Adiels, M.

AU - Söderlund, S.

AU - Chan, D.C.

AU - Hakkarainen, A.

AU - Lundbom, N.

AU - Matikainen, N.

AU - Kahri, J.

AU - Vergès, B.

AU - Barrett, Hugh

AU - Taskinen, M.R.

PY - 2015/10

Y1 - 2015/10

N2 - © 2015 American Heart Association, Inc. Objectives-Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. Approach and Results-A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, P>0.01; r=0.45, P>0.01) and fractional catabolism (r=0.49, P>0.001; r=0.55, P>0.001) of VLDL1-triglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, P>0.001) and VLDL1-apoB (r=0.53, P>0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL1-triglycerides (r=0.48, P>0.001) and VLDL1-apoB (r=0.51, P>0.001). Conclusions-Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity.

AB - © 2015 American Heart Association, Inc. Objectives-Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. Approach and Results-A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, P>0.01; r=0.45, P>0.01) and fractional catabolism (r=0.49, P>0.001; r=0.55, P>0.001) of VLDL1-triglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, P>0.001) and VLDL1-apoB (r=0.53, P>0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL1-triglycerides (r=0.48, P>0.001) and VLDL1-apoB (r=0.51, P>0.001). Conclusions-Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity.

U2 - 10.1161/ATVBAHA.115.305614

DO - 10.1161/ATVBAHA.115.305614

M3 - Article

VL - 35

SP - 2218

EP - 2224

JO - ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

JF - ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

SN - 1079-5642

IS - 10

ER -