Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.

Vu‐Dac, Ngoc; Schoonjans, Kristina; Kosykh, V. P.; Dallongeville, Jean; Fruchart, Jean‐Charles; Staels, Bart; Auwerx, Johan

doi:10.1172/jci118118

Cited by 366 publications

(222 citation statements)

References 84 publications

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“…Previous studies had shown that fibrates increased human apoAII expression through activation of peroxisome proliferator-activated receptors ␣ in HCV-negative HepG2 cells. 34 We verified that peroxisome proliferator-activated receptors ␣ expression was maintained in HCV-positive HepG2 cells (data not shown). We also verified whether fenofibric acid could induce apoAII messenger RNA accumulation.…”

Section: Effect Of Fenofibric Acid On Apoaii Messenger Rna Accumulationmentioning

confidence: 60%

“…In order to clarify further the biological relevance of this interaction, we took advantage of the well-established increase in apoAII expression caused in HepG2 cells by fibrates. 34 We show here with the modulation of HCV core secretion brought about by the treatment with fenofibric acid of 2 independent clones of a HepG2 cell stably expressing the HCV core protein. Overall, our data identified apoAII as one of the cellular targets of HCV core protein and showed the direct impact of cellular lipid metabolism on HCV core protein secretion.…”

mentioning

confidence: 94%

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Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

et al. 1999

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Hepatitis C virus (HCV) is the major etiologic agent of post-transfusion and sporadic non-A, non-B hepatitis. 1 Persistent HCV infection, which develops in at least 70% to 80% of infected patients, often progresses to chronic hepatitis and is highly correlated with the development of cirrhosis and hepatocellular carcinoma. 2-4 Neither a vaccine, nor effective therapy are currently available for HCV, other than interferon alfa combined with ribavirin. 5,6

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Section: Effect Of Fenofibric Acid On Apoaii Messenger Rna Accumulationmentioning

confidence: 60%

mentioning

confidence: 94%

Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

et al. 1999

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“…Synthesis of apo A-I and apo A-II, the two major proteins of HDL, by the liver and intestine is the first step in HDL particle formation. PPAR-␣ activation by fibrates activates human apo A-I and apo A-II genes in the liver, leading to increased synthesis of these proteins (95)(96)(97)(98). A recent study (36) using rabbits expressing the human apo A-I transgene along with its PPRE showed an increase in human apo A-I mRNA and mass in response to fenofibrate treatment in the absence of any peroxisome-proliferative effect of the fibrate.…”

Section: Ppar-␣ Effects On Tg Ldl and Hdl Metabolismmentioning

confidence: 99%

PPAR-α effects on the heart and other vascular tissues

Francis

Annicotte²,

Auwerx³

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Peroxisome proliferator-activated receptor (PPAR)-α is a member of a large nuclear receptor superfamily whose main role is to activate genes involved in fatty acid oxidation in the liver, heart, kidney, and skeletal muscle. While currently used mainly as hypolipidemic agents, the cardiac effects and anti-inflammatory actions of PPAR-α agonists in arterial wall cells suggest other potential cardioprotective and antiatherosclerotic effects of these agents. This review summarizes current knowledge regarding the effects of PPAR-α agonists on lipid and lipoprotein metabolism, the heart, and the vessel wall and introduces some of the insights gained in these areas from studying PPAR-α-deficient mice. The introduction of new and more potent PPAR-α agonists will provide important insights into the overall benefits of activating PPAR-α clinically for the treatment of dyslipidemia and prevention of vascular disease.

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“…18 In addition, the fenofibrate treatment caused small but not statistically significant changes in the expression of mouse Apoc3, Apoa2, Apoa5 and Apoe genes, as well as in other genes that are involved in the biogenesis and maturation of HDL such as Abca1, Lcat and Abcg1 (Table 1). Overall, the increase in HDL could not be accounted for by the upregulation of Apoa1 and Apoa2 as suggested previously 20,21 or attributed to the changes in several other genes implicated in the biogenesis of HDL.…”

Section: Discussionmentioning

confidence: 44%

“…9,10 Fibrates were shown to promote b-oxidation of fatty acids (FA) by upregulating various genes, including several genes of FA uptake and b-oxidation. [11][12][13][14][15][16][17][18][19] In rodents, fibrates downregulated the expression of Apoa1, 20 hepatic lipase 13 and lecithin cholesterol acyltransferase (Lcat) 15 genes and upregulated the expression of Apoa2 21 and phospholipid transfer protein (Pltp). 22 Previous studies of human ApoA-I transgenic Mice and rabbits indicated that fenofibrate increase plasma ApoA-I and HDL levels.…”

Section: Introductionmentioning

confidence: 99%

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

et al. 2009

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We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and b-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.

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Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.

Abstract: In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use

Cited by 366 publications

References 84 publications

Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

PPAR-α effects on the heart and other vascular tissues

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

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