The hyperenergetic-fed obese dog, a model of disturbance of apolipoprotein B-100 metabolism associated with insulin resistance: kinetic study using stable isotopes.
The hyperenergetic-fed beagle dog model of obesity-associated insulin resistance has previously demonstrated lipoprotein abnormalities similar to those of obese insulin-resistant humans. The aim of this study was to check, in the insulin-resistant dog, the mechanism leading to abnormalities in the mass of apolipoprotein B-100 (apo B-100) containing lipoproteins. Six healthy male beagle dogs were overfed with a high-fat diet for 28 +/- 2.5 weeks. Obesity was associated with insulin resistance as assessed by the euglycemic hyperinsulinemic clamp technique. The kinetics of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) apo B-100 were recorded in dogs, at healthy and insulin-resistant states, using a primed constant infusion of [5,5,5-D(3)]leucine. Isotopic enrichment was measured by gas chromatography-mass spectrometry (GC-MS). A multicompartmental model was used for the analysis of tracer kinetics data. Apolipoprotein B-100 concentration was higher in VLDL (2.8-fold, P < .05) but lower in LDL (2-fold, P < .05) in the insulin-resistant compared to the healthy state. Kinetic analysis showed a higher VLDL apo B-100 production (1.7-fold, P < .05). The fractional catabolic rate of VLDL did not change significantly, but the lipolysis was decreased significantly (3-fold, P < .05). The lower LDL apo B-100 level in insulin-resistant dogs was explained by a higher LDL fractional catabolic rate (2.5-fold, P < .05). The mechanisms leading to hypertriglyceridemia (higher production rate and lower lipolysis of VLDL) in insulin-resistant dogs were similar to those described in the insulin-resistant humans.
Centre de Recherche en Nutrition Humaine, Institut national de la santé et de la recherche médicale, INSERM U539, CHU Nantes F-44000, France.
François
F
Briand
Edwige
E
Bailhache
Agnes
A
Andre
Thierry
T
Magot
Michel
M
Krempf
Patrick
P
Nguyen
Khadija
K
Ouguerram
D000818:Animals; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004285:Dogs; D002149:Energy Intake / Q000502:physiology*; D008401:Gas Chromatography-Mass Spectrometry; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D009765:Obesity / Q000097:blood / Q000378:metabolism*
D053299:Apolipoprotein B-100; D001786:Blood Glucose; D007328:Insulin; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D007930:Leucine