Roles of peroxisome proliferator-activated receptor delta (PPARδ) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome

Luquet, Serge; López‐Soriano, Joaquín; Holst, Dorte; Gaudel, Céline; Jehl-Piétri, Chantal; Fredenrich, A.; Grimaldi, Paul A.

doi:10.1016/j.biochi.2004.09.024

Cited by 86 publications

(68 citation statements)

References 26 publications

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“…cPGI, a stable analogue of PGI 2 , and GW501516, a selective synthetic agonist of PPARy, activate PPARy in a variety of cell lines (24,30,31). Therefore, we examined the ability of cPGI or GW501516 to activate PPARy in T2 and OVCAR3 cell lines using a PPARy-LBD-GAL4 ligand-binding reporter assay (24,32).…”

Section: Resultsmentioning

confidence: 99%

Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer

Daikoku¹,

Tranguch²,

Chakrabarty³

et al. 2007

Cancer Research

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The underlying causes of epithelial ovarian cancer (EOC) are unclear, and treatment options for patients with advanced disease are limited. There is evidence that the use of nonsteroidal anti-inflammatory drugs is associated with decreased risk of developing EOC. Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX)-1 and COX-2, which catalyze prostaglandin biosynthesis. We previously showed that mouse and human EOCs have increased levels of COX-1, but not COX-2, and a COX-1-selective inhibitor, SC-560, attenuates prostaglandin production and tumor growth. However, the downstream targets of COX-1 signaling in EOC are not yet known. To address this question, we evaluated peroxisome proliferator-activated receptor D (PPARD) expression and function in EOC. We found that EOC cells express high levels of PPARD, and neutralizing PPARD function reduces tumor growth in vivo. More interestingly, aspirin, a nonsteroidal anti-inflammatory drug that preferentially inhibits COX-1, compromises PPARD function and cell growth by inhibiting extracellular signal-regulated kinases 1/2, members of the mitogen-activated protein kinase family. Our study, for the first time, shows that whereas PPARD can be a target of COX-1, extracellular signal-regulated kinase is a potential target of PPARD. The ability of aspirin to inhibit EOC growth in vivo is an exciting finding because of its low cost, lack of cardiovascular side effects, and availability. [Cancer Res 2007;67(11):5285-92]

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Section: Resultsmentioning

confidence: 99%

Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer

Daikoku¹,

Tranguch²,

Chakrabarty³

et al. 2007

Cancer Research

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“…PPARα is expressed most abundantly in the liver where oxidation occurs in the mitochondria and peroxisomes (5). PPARβ/δ, which is expressed ubiquitously (6), activates genes of fatty acid oxidation (7) and is a target for the treatment of metabolic syndrome (8), cardiomyopathy (9), cholesterol metabolism (10), colon carcinogenesis (11), and obesity (12). PPARγ is a transcription factor expressed selectively in adipose tissue (13) and seems to be associated with adipocyte differentiation.…”

Section: Introductionmentioning

confidence: 99%

CLOCK/BMAL1 is Involved in Lipid Metabolism via Transactivation of the Peroxisome Proliferator-activated Receptor (PPAR) Response Element

Inoue

Shinoda

Ikeda

et al. 2005

JAT

125

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Lipid absorption and metabolism are regulated by feeding and by the circadian system. It has been suggested that the expression of enzymes involved in lipid metabolism is directly controlled by the clock system. This study was designed to examine whether or not the CLOCK/BMAL1 heterodimer has transcriptional activity for genes via the peroxisome proliferator-activated receptor response element (PPRE).

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“…Treatment with a synthetic PPAR␦ agonist substantially improved lipid profiles in mice and monkeys and inhibited diet-induced obesity and insulin resistance by increasing the expression of genes that promote lipid catabolism and mitochondrial uncoupling (7,(9)(10)(11)(12)(13). Moreover, adipose tissuespecific overexpression of PPAR␦ prevented the development of obesity in db/db mice (9).…”

mentioning

confidence: 99%

PPARδ-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis

Takata

Liu

Yin

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

197

181

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Activation of the nuclear hormone receptor peroxisome proliferatoractivated receptor ␦ (PPAR␦) has been shown to improve insulin resistance, adiposity, and plasma HDL levels. However, its antiatherogenic role remains controversial. Here we report atheroprotective effects of PPAR␦ activation in a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by increased vascular inflammation related to repression of an antiinflammatory corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the PPAR␦ agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII-accelerated atherosclerosis without altering blood pressure and increased vascular expression of Bcl-6, RGS4, and RGS5, which was associated with suppression of inflammatory and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated macrophages: PPAR␦ activation increased both total and free Bcl-6 levels and inhibited AngII activation of MAP kinases, p38, and ERK1/2. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of PPAR␦ activation to inhibit AngII signaling, which is atheroprotective.peroxisome proliferator-activated receptor ␦ ͉ vascular inflammation ͉ macrophage

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Roles of peroxisome proliferator-activated receptor delta (PPARδ) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome

Cited by 86 publications

References 26 publications

Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer

Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer

CLOCK/BMAL1 is Involved in Lipid Metabolism via Transactivation of the Peroxisome Proliferator-activated Receptor (PPAR) Response Element

PPARδ-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis

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