title: Increased VLDL-triglyceride secretion precedes impaired control of endogenous glucose production in obese, normoglycemic men.
abstract: OBJECTIVE
  To assess basal and insulin-mediated VLDL-triglyceride (TG) kinetics and the relationship between VLDL-TG secretion and hepatic insulin resistance assessed by endogenous glucose production (EGP) in obese and lean men.
  
  
  METHODS
  A total of 12 normoglycemic, obese (waist-to-hip ratio >0.9, BMI >30 kg/m(2)) and 12 lean (BMI 20-25 kg/m(2)) age-matched men were included. Ex vivo-labeled [1-(14)C]VLDL-TGs and [3-(3)H]glucose were infused postabsorptively and during a hyperinsulinemic-euglycemic clamp to determine VLDL-TG kinetics and EGP. Body composition was determined by dual X-ray absorptiometry and computed tomography scanning. Energy expenditure and substrate oxidation rates were measured by indirect calorimetry.
  
  
  RESULTS
  Basal VLDL-TG secretion rates were increased in obese compared with lean men (1.25 ± 0.34 vs. 0.86 ± 0.34 μmol/kg fat-free mass [FFM]/min; P = 0.011), whereas there was no difference in clearance rates (150 ± 56 vs. 162 ± 77 mL/min; P = NS), resulting in greater VLDL-TG concentrations (0.74 ± 0.40 vs. 0.38 ± 0.20 mmol/L; P = 0.011). The absolute insulin-mediated suppression of VLDL-TG secretion was similar in the groups. However, the percentage reduction (-36 ± 18 vs. -54 ± 10%; P = 0.008) and achieved VLDL-TG secretion rates (0.76 ± 0.20 vs. 0.41 ± 0.19 μmol/kg FFM/min; P < 0.001) were impaired in obese men. Furthermore, clearance rates decreased significantly in obese men, but there was no significant change in lean men (-17 ± 18 vs. 7 ± 20%; P = 0.007), resulting in less percentage reduction of VLDL-TG concentrations in obese men (-22 ± 20 vs. -56 ± 11%; P < 0.001). Insulin-suppressed EGP was similar (0.4 [0.0-0.8] vs. 0.1 [0.0-1.2] mg/kg FFM/min (median [range]); P = NS), and the percentage reduction was equivalent (-80% [57-98] vs. -98% [49-100], P = NS). Insulin-mediated glucose disposal was significantly reduced in obese men.
  
  
  CONCLUSIONS
  Basal VLDL-TG secretion rates are increased in normoglycemic but insulin-resistant, obese men, resulting in hypertriglyceridemia. Insulin-mediated suppression of EGP is preserved in obese men, whereas suppression of VLDL-TG secretion is less pronounced in obese men. Compared with EGP, the inability to achieve suppression of VLDL-TG secretions to a level similar to control subjects during hyperinsulinemia seems to be an early manifestation in male obesity.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Sørensen
authors.forename: Esben
authors.initials: E
authors.lastname: Søndergaard
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nellemann
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Lars C
authors.initials: LC
authors.lastname: Gormsen
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D002153:Calorimetry, Indirect; D015243:Cholesterol, VLDL / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D015243:Cholesterol, VLDL; D014280:Triglycerides; D005947:Glucose