Rosiglitazone modifies HDL structure and increases HDL-apo AI synthesis and catabolic rates

Carreón‐Torres, Elizabeth; Rendón-Sauer, Karla; Monter-Garrido, Mariana; Toledo-Ibelles, Paola; Gamboa, Ricardo; Márta, Mészáros; López‐Marure, Rebeca; Luc, Gérald; Fiévet, Catherine; Cruz, David; Vargas‐Alarcón, Gilberto; Pérez-Méndez, Óscar

doi:10.1016/j.cca.2008.11.003

Cited by 28 publications

(23 citation statements)

References 33 publications

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“…Weak, partial transactivation of PPAR ␣ by rosiglitazone ( 15,16 ) and pioglitazone ( 16,17 ) has been demonstrated in vitro and may result in upregulation of the PPAR ␣ targets apoA-I and apoA-II, leading to an increase in the production rates (PRs) of these proteins. Consistent with these in vitro fi ndings, Carreon-Torres et al ( 18 ) recently reported that rosiglitazone increased apoA-I production in rabbits. In contrast, a study in patients with type 2 diabetes demonstrated that treatment with pioglitazone had no effect on apoA-I kinetics ( 19 ).…”

Section: Cellular Cholesterol Effl Ux Studiessupporting

confidence: 66%

“…Initial studies with rosiglitazone in rats examined the mechanisms responsible for its lipid-altering effects and concluded that there was no signifi cant transactivation of PPAR ␣ in liver ( 26 ). However, subsequent reports have indicated that rosiglitazone increases apoA-I production in rabbits ( 18 ) and the human hepatoma cell line, HepG2 ( 16 ), via partial activation of PPAR ␣ . We found that there was no change in the PR of the PPAR ␣ target apoA-I following rosiglitazone treatment.…”

Section: Determinants Of the Change In Hdl-c Levelsmentioning

confidence: 99%

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Effect of rosiglitazone on HDL metabolism in subjects with metabolic syndrome and low HDL

Millar

Ikewaki

Bloedon

et al. 2011

Journal of Lipid Research

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The metabolic syndrome consists of a cluster of abnormalities that include hypertension, abdominal obesity, impaired fasting glucose, elevated fasting triglyceride levels, and low HDL-cholesterol (HDL-C). Patients with metabolic syndrome are at increased risk of cardiovascular disease and, as a result, recommendations have been made to reduce the risk in these patients. These recommendations include therapeutic lifestyle changes and, if treatment goals are not met, pharmacological intervention ( 1 ).Currently, few drugs are available that are suitable for treating patients with two components of the metabolic syndrome, insulin resistance and low HDL-C. Among treatments available for improving insulin resistance are the thiazolidinediones (TZDs) rosiglitazone and pioglitazone, which activate the nuclear receptor peroxisome proliferatoractivated receptor ␥ (PPAR ␥ ). In addition to their insulinsensitizing effects, TZDs have been shown to increase HDL-C levels in diabetic populations ( 2 ) by up to 14% for rosiglitazone and up to 19% for pioglitazone ( 3 ). These changes in HDL-C compare favorably to HDL-C changes achieved with other drugs currently approved to treat low HDL-C levels ( 4-7 ). Although rosiglitazone and pioglitazone both activate PPAR ␥ , they each have a characteristic metabolic response in regard to plasma lipid levels, with rosiglitazone also increasing plasma triglyceride levels in the relatively short term, whereas pioglitazone does not ( 8 ).The mechanisms responsible for the HDL-C-raising effects of TZDs are currently unknown. Studies that have measured apolipoprotein A-I (apoA-I) and apoA-II levels Abstract Treatment with the peroxisome proliferator-activated receptor ␥ 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 signifi cantly 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 signifi cantly correlated with the change in apoA-II concentration but not to changes in apoA-I, measures of glucose homeostasis, or hsCRP. Treatment with rosiglitazone signifi cantly 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 u...

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Section: Cellular Cholesterol Effl Ux Studiessupporting

confidence: 66%

Section: Determinants Of the Change In Hdl-c Levelsmentioning

confidence: 99%

Effect of rosiglitazone on HDL metabolism in subjects with metabolic syndrome and low HDL

Millar

Ikewaki

Bloedon

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

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“…These findings are consistent with the increased levels of HDL-triacylglycerols observed in rabbits during proteinuria. In this context, HDL structure is related to the metabolism of these lipoproteins [6,7,24,44,45]; notably, small HDL appear to be catabolized faster than larger particles [36,37,44,45]. In this study, the increased apo A-I FCR observed in proteinuric rabbits further supports the augmented loss of small HDL via the kidney.…”

Section: Discussionsupporting

confidence: 74%

Increased HDL Size and Enhanced Apo A‐I Catabolic Rates Are Associated With Doxorubicin‐Induced Proteinuria in New Zealand White Rabbits

López-Olmos

Carreón‐Torres

Luna-Luna

et al. 2016

Lipids

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The catabolism and structure of high-density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A-I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL-apo A-I was evaluated by exogenous radiolabelling with iodine-131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol-to-phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [(131)I]-apo A-I in the proteinuric rabbits was faster (FCR = 0.036 h(-1)) compared to control rabbits group (FCR = 0.026 h(-1), P < 0.05). Apo E increased and apo A-I decreased in HDL, whereas PON-1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase-1 activity, and a rise in the fractional catabolic rate of the [(131)I]-apo A-I.

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“…First, in a study of 19 human subjects with Type 2 diabetes, rosiglitazone was found to increase fasting and postprandial PON1 activity [136]. Additional studies in rabbits [137] and rats [138] demonstrated similar results as those found in humans: the rabbits had a 21% increase in serum PON1 activity after 6 weeks of rosiglitazone therapy [137], while the rats exhibited a 68% increase in hepatic PON1 activity after 2 weeks of rosiglitazone therapy immediately following 6 weeks of a high-fructose diet used to mimic metabolic syndrome [138]. …”

Section: Pharmacologic Determinants Of Pon1 Levels And/or Activitymentioning

confidence: 99%

Pharmacogenetics of Paraoxonase Activity: Elucidating the Role of High-Density Lipoprotein in Disease

et al. 2013

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PON1 is a key component of high-density lipoproteins (HDLs) and is at least partially responsible for HDL's antioxidant/atheroprotective properties. PON1 is also associated with numerous human diseases, including cardiovascular disease, Parkinson's disease and cancer. In addition, PON1 metabolizes a broad variety of substrates, including toxic organophosphorous compounds, statin adducts, glucocorticoids, the likely atherogenic l-homocysteine thiolactone and the quorum-sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and antioxidant supplements affect PON1 expression and enzyme activity levels. Owing to the importance of PON1 to HDL function and its individual association with diverse human diseases, pharmacogenomic interactions between PON1 and the various factors that alter its expression and activity may represent an important therapeutic target for future investigation.

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Rosiglitazone modifies HDL structure and increases HDL-apo AI synthesis and catabolic rates

Cited by 28 publications

References 33 publications

Effect of rosiglitazone on HDL metabolism in subjects with metabolic syndrome and low HDL

Effect of rosiglitazone on HDL metabolism in subjects with metabolic syndrome and low HDL

Increased HDL Size and Enhanced Apo A‐I Catabolic Rates Are Associated With Doxorubicin‐Induced Proteinuria in New Zealand White Rabbits

Pharmacogenetics of Paraoxonase Activity: Elucidating the Role of High-Density Lipoprotein in Disease

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