title: Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity: Multicenter Tracer Kinetic Study.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.). jan.boren@wlab.gu.se.
authors: Jan
authors: J
authors: Borén
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Gerald F
authors: GF
authors: Watts
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Martin
authors: M
authors: Adiels
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Sanni
authors: S
authors: Söderlund
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Dick C
authors: DC
authors: Chan
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Antti
authors: A
authors: Hakkarainen
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Nina
authors: N
authors: Lundbom
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Niina
authors: N
authors: Matikainen
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Juhani
authors: J
authors: Kahri
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Bruno
authors: B
authors: Vergès
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: P Hugh R
authors: PH
authors: Barrett
authors: From the Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden (J.B., M.A.); Lipid Disorders Clinic, Metabolic Research Centre, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology (G.F.W., D.C.C., P.H.R.B.) and Faculty of Engineering, Computing and Mathematics (P.H.R.B.), University of Western Australia, Perth, Australia; Heart and Lung Centre, Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity (S.S., N.M., M.-R.T.) and Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital (A.H., N.L.), University of Helsinki, Helsinki, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (N.M., J.K.); and Department of Endocrinology-Diabetology, University Hospital and INSERM CRI 866, Dijon, France (B.V.).
authors: Marja-Riitta
authors: MR
authors: Taskinen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D053305:Apolipoprotein C-III / Q000097:blood*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D015331:Cohort Studies; D050171:Dyslipidemias / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D056128:Obesity, Abdominal / Q000097:blood* / Q000150:complications; D009929:Organ Size; D011849:Radioactive Tracers; D012016:Reference Values; D018570:Risk Assessment; D014280:Triglycerides / Q000097:blood*
chemical_list: D053305:Apolipoprotein C-III; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011849:Radioactive Tracers; D014280:Triglycerides; C030087:lipoprotein triglyceride; C030106:very low density lipoprotein triglyceride
keywords: apolipoproteins B; cardiovascular disease; kinetics; multicompartmental modeling; obesity; triglycerides