Abstract
Treatment with the peroxisome proliferator-activated receptor γ agonist rosiglitazone has been reported to increase HDL-cholesterol (HDL-C) levels, although the mechanism responsible for this is unknown. We sought to determine the effect of rosiglitazone on HDL apolipoprotein A-I (apoA-I) and apoA-II metabolism in subjects with metabolic syndrome and low HDL-C. Subjects were treated with placebo followed by rosiglitazone (8 mg) once daily. At the end of each 8 week treatment, subjects (n = 15) underwent a kinetic study to measure apoA-I and apoA-II production rate (PR) and fractional catabolic rate. Rosiglitazone significantly reduced fasting insulin and high-sensitivity C-reactive protein (hsCRP) and increased apoA-II levels. Mean apoA-I and HDL-C levels were unchanged following rosiglitazone treatment, although there was considerable individual variability in the HDL-C response. Rosiglitazone had no effect on apoA-I metabolism, whereas the apoA-II PR was increased by 23%. The change in HDL-C in response to rosiglitazone was significantly correlated with the change in apoA-II concentration but not to changes in apoA-I, measures of glucose homeostasis, or hsCRP. Treatment with rosiglitazone significantly increased apoA-II production in subjects with metabolic syndrome and low HDL-C but had no effect on apoA-I metabolism. The change in HDL-C in response to rosiglitazone treatment was unrelated to effects on apoA-I, instead being related to the change in the metabolism of apoA-II.
Highlights
Treatment with the peroxisome proliferator-activated receptor ␥ agonist rosiglitazone has been reported to increase HDL-cholesterol (HDL-C) levels, the mechanism responsible for this is unknown
Similar to what was reported for pioglitazone [19], the results show that the metabolism of apolipoprotein A-I (apoA-I) was unchanged in response to rosiglitazone treatment, whereas there was a significant increase in the production rate (PR) of apoA-II
We found that there was no change in the PR of the PPAR␣ target apoA-I following rosiglitazone treatment
Summary
Treatment with the peroxisome proliferator-activated receptor ␥ agonist rosiglitazone has been reported to increase HDL-cholesterol (HDL-C) levels, the mechanism responsible for this is unknown. We sought to determine the effect of rosiglitazone on HDL apolipoprotein A-I (apoA-I) and apoA-II metabolism in subjects with metabolic syndrome and low HDL-C. Mean apoA-I and HDL-C levels were unchanged following rosiglitazone treatment, there was considerable individual variability in the HDL-C response. The change in HDL-C in response to rosiglitazone was significantly correlated with the change in apoA-II concentration but not to changes in apoA-I, measures of glucose homeostasis, or hsCRP. Treatment with rosiglitazone significantly increased apoA-II production in subjects with metabolic syndrome and low HDL-C but had no effect on apoA-I metabolism. The change in HDL-C in response to rosiglitazone treatment was unrelated to effects on apoA-I, instead being related to the change in the metabolism of apoA-II.—Millar, J. Effect of rosiglitazone on HDL metabolism in subjects with metabolic syndrome and low HDL.
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