title: Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Nonalcoholic Fatty Liver Disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of very low-density lipoprotein-triglyceride (VLDL-TG) kinetics is not fully understood.
  
  
  
  The objective of the study was to determine VLDL-TG, glucose, and palmitate kinetics during fasting and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD−).
  
  
  
  Twenty-seven nondiabetic, upper-body obese (waist to hip ratio > 0.9, body mass index > 28 kg/m2) men, 18 NAFLD+, and nine NAFLD− determined by magnetic resonance spectroscopy were enrolled.14C-labeled VLDL-TG and 3H-labeled glucose and palmitate tracers were applied in combination with indirect calorimetry and breath samples to assess kinetics and substrate oxidations postabsorptively and during a hyperinsulinemic-euglycemic clamp. Dual-X-ray absorptiometry and magnetic resonance imaging assessed body composition.
  
  
  
  Liver fat content was greater in NAFLD+ than NAFLD− men (21.0% vs 3.7%), even though body composition, metabolites (except triglycerides), and insulin were similar in the groups. Insulin suppression of VLDL-TG secretion (P = .0001), oxidation (P = .0003), and concentration (P= .008) as well as percentage decreases were lower in NAFLD+ than NAFLD− men (secretion: 31.9% ± 17.2% vs 64.7% ± 19.9%; oxidation: −9.0% ± 24.7% vs 46.5% ± 36.6%; concentration: 11.9% ± 20.7% vs 56.2% ± 22.9%, all P < .001). Likewise, lower insulin suppression of very low-density lipoprotein particle size was present in NAFLD+ than NAFLD− men (P = .0002). Conversely, insulin suppression of endogenous glucose production was similar in the groups.
  
  
  
  Compared with endogenous glucose production, the inability of NAFLD+ men to suppress VLDL-TG kinetics to compensate for the increased liver fat content seems to be an early pathophysiological manifestation of male NAFLD+. These data suggest therapeutic targets reducing liver fat content may ameliorate metabolic abnormalities associated with NAFLD and presumably diabetes.
authors.affiliation: Departments of Endocrinology and Internal Medicine (M.K.P., B.N., S.B.P., S.N.) and Hepatology and Gastroenterology (H.G.), Aarhus University Hospital, 8000 C Aarhus, Denmark; and The MR Research Centre (H.S.-J.), Aarhus University Hospital, 8200 N Skejby, Denmark.
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Poulsen
authors.affiliation: Departments of Endocrinology and Internal Medicine (M.K.P., B.N., S.B.P., S.N.) and Hepatology and Gastroenterology (H.G.), Aarhus University Hospital, 8000 C Aarhus, Denmark; and The MR Research Centre (H.S.-J.), Aarhus University Hospital, 8200 N Skejby, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nellemann
authors.affiliation: Departments of Endocrinology and Internal Medicine (M.K.P., B.N., S.B.P., S.N.) and Hepatology and Gastroenterology (H.G.), Aarhus University Hospital, 8000 C Aarhus, Denmark; and The MR Research Centre (H.S.-J.), Aarhus University Hospital, 8200 N Skejby, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Stødkilde-Jørgensen
authors.affiliation: Departments of Endocrinology and Internal Medicine (M.K.P., B.N., S.B.P., S.N.) and Hepatology and Gastroenterology (H.G.), Aarhus University Hospital, 8000 C Aarhus, Denmark; and The MR Research Centre (H.S.-J.), Aarhus University Hospital, 8200 N Skejby, Denmark.
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: Departments of Endocrinology and Internal Medicine (M.K.P., B.N., S.B.P., S.N.) and Hepatology and Gastroenterology (H.G.), Aarhus University Hospital, 8000 C Aarhus, Denmark; and The MR Research Centre (H.S.-J.), Aarhus University Hospital, 8200 N Skejby, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbæk
authors.affiliation: Departments of Endocrinology and Internal Medicine (M.K.P., B.N., S.B.P., S.N.) and Hepatology and Gastroenterology (H.G.), Aarhus University Hospital, 8000 C Aarhus, Denmark; and The MR Research Centre (H.S.-J.), Aarhus University Hospital, 8200 N Skejby, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000503:physiopathology*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride