High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study.
OBJECTIVE
Mechanisms responsible for the decreased high-density lipoprotein (HDL) cholesterol level associated with insulin resistance in obese patients are not clearly understood. To determine the influence of insulin resistance at an early stage on HDL metabolism, we performed a stable isotope kinetic study of apolipoprotein (apo) A-I, in five obese insulin resistant women with normal fasting triglycerides and without impaired glucose tolerance, and in five age-matched control women.


METHODS
Each subject received a 16 h constant infusion of L-[1-(13)C]leucine at 0.7 mg/kg/h following a primed bolus of 0.7 mg/kg.


RESULTS
ApoA-I fractional catabolic rate (FCR) was significantly increased in insulin-resistant women compared to controls (0.316+/-0.056 vs 0.210+/-0.040 per day, P<0.01), indicating a significant 50% increase of apoA-I catabolism, leading to an important reduction of plasma apoA-I residence time (3.25+/-0.59 vs 4.92+/-1.11, P<0.01). ApoA-I production rate tended to be higher in insulin resistant women than in controls (364+/-77 vs 258+/-60 mg/l/day, P=0.13), but the difference was not statistically significant. ApoA-I FCR was correlated with triglycerides during the fed state (r=0.69; P=0.026) and HDL triglycerides-esterified cholesterol ratio (r=0.73; P=0.016), suggesting that alteration of apoA-I metabolism in insulin resistance may be partly related to HDL enrichment in triglycerides.


CONCLUSIONS
Our kinetic study shows that patients, at an early stage of insulin resistance (without impaired glucose tolerance nor fasting hypertriglyceridaemia), already have a significant alteration of apoA-I metabolism (increased apoA-I catabolism), which is consistent with the increased risk of atherosclerosis in this population.
Laboratoire de Biochimie des Lipoprotéines, INSERM U 498, Faculté de Médecine, Dijon, France.
F
F
Pont
L
L
Duvillard
E
E
Florentin
P
P
Gambert
B
B
Vergès
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007554:Isotopes / Q000008:administration & dosage / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000008:administration & dosage; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D015233:Models, Statistical; D009765:Obesity / Q000503:physiopathology*; D013997:Time Factors
D016632:Apolipoprotein A-I; D007554:Isotopes; D008075:Lipoproteins, HDL; D007930:Leucine