Regulation of the peroxisomal β-oxidation-dependent pathway by peroxisome proliferator-activated receptor α and kinases

Latruffe, Norbert; Cherkaoui-Malki, Mustapha; Nicolas-Francès, Valérie; Clémencet, Marie-Claude; Jannin, Brigitte; Berlot, Jean-Pierre

doi:10.1016/s0006-2952(00)00416-0

Cited by 74 publications

(46 citation statements)

References 42 publications

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“…Additionally, we confirmed that p300, which is a major coactivator for PPAR␣ in small intestine (48), was also up-regulated by caprylic acid in weanling rats (49). Considering that PPAR␣ activates ␤-oxidation in many organs (50), caprylic acid may have some function in activating ␤-oxidation in the postnatal small intestine through enhancing gene expression of PPAR␣ as well as p300 and RXR␣ which are components of the PPAR␣-dependent transcriptional machinery. The results of the current study suggest that fatty acids in milk may alter the function of the small intestine to allow effective absorption of dietary fat and vitamin A by inducing L-FABP and CRBPII through PPAR␣.…”

Section: )supporting

confidence: 70%

Possible Role of Fatty Acids in Milk as the Regulator of the Expression of Cytosolic Binding Proteins for Fatty Acids and Vitamin A through PPAR.ALPHA. in Developing Rats

Mochizuki

Kawai

et al. 2007

J Nutr Sci Vitaminol

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Summary Fatty acids in milk are thought to play an important role in intestinal maturation and gene expression in the postnatal small intestine. In this study, we determined the jejunal mRNA levels, in rats, of peroxisome proliferator-activated receptor ␣ (PPAR ␣ ) and PPAR ␦ which are nuclear receptors for fatty acids. We also measured expression of their target genes during the postnatal period, namely liver type fatty acid-binding protein (L-FABP) and cellular retinol-binding protein, type II (CRBPII). The mRNA levels of PPAR ␣ , L-FABP and CRBPII, but not PPAR ␦ , gradually increased during the suckling period and then sharply declined to a low level at the end of the weaning period. Rat pups at 17 d of age, weaned to a high-fat diet, showed significantly greater mRNA levels of PPAR ␣ , L-FABP and CRBPII than those weaned to a low-fat diet. Oral administration of PPAR ␣ ligand, WY14,643 during four consecutive days of the weanling period caused a parallel increase in the mRNA levels of PPAR ␣ , L-FABP and CRBPII genes. Furthermore, caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPAR ␣ , L-FABP and CRBPII gene expression. Our results suggest that fatty acids in milk may play a pivotal role in maintaining an enhanced level of expression of L-FABP and CRBPII genes in the small intestine, presumably by acting as inducers of PPAR ␣ gene expression.

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Section: )supporting

confidence: 70%

Possible Role of Fatty Acids in Milk as the Regulator of the Expression of Cytosolic Binding Proteins for Fatty Acids and Vitamin A through PPAR.ALPHA. in Developing Rats

Mochizuki

Kawai

et al. 2007

J Nutr Sci Vitaminol

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“…37 Secondly, and more gradually, oxidase activity can also be modulated by upregulation of the expression levels of one or more NADPH oxidase component subunits. To date, it is unclear whether stimulation of PKC activity or increase in fatty acid catabolism 38 could be implicated in the effects of PPAR-␣ agonists. However, phorbol myristate acetate or angiotensin II activation of macrophages increases ROS production within 15 to 20 minutes, whereas PPAR-␣ activators require a longer time with a maximum around 16 to 24 hours, suggesting that p47 phox , p67 phox and gp91 phox mRNA levels may be functionally significant.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator–Activated Receptor α Induces NADPH Oxidase Activity in Macrophages, Leading to the Generation of LDL with PPAR-α Activation Properties

Teissier

Nohara

Chinetti-Gbaguidi

et al. 2004

Circulation Research

113

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Abstract-Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors controlling lipid and glucose metabolism as well as inflammation. PPARs are expressed in macrophages, cells that also generate reactive oxygen species (ROS). In this study, we investigated whether PPARs regulate ROS production in macrophages. Different PPAR-␣, but not PPAR-␥ agonists, increased the production of ROS (H 2 O 2 and O 2 . ) in human and murine macrophages.PPAR-␣ activation did not induce cellular toxicity, but significantly decreased intracellular glutathione levels. The increase in ROS production was not attributable to inherent prooxidant effects of the PPAR-␣ agonists tested, but was mediated by PPAR-␣, because the effects were lost in bone marrow-derived macrophages from PPAR-␣ Ϫ/Ϫ mice. The PPAR-␣-induced increase in ROS was attributable to the induction of NADPH oxidase, because (1) preincubation with the NADPH oxidase inhibitor diphenyleneiodinium prevented the increase in ROS production; (2) PPAR-␣ agonists increased O 2 . production measured by superoxide dismutase-inhibitable cytochrome c reduction; (3) PPAR-␣ agonists induced mRNA levels of the NADPH oxidase subunits p47 phox , p67 phox , and gp91 phox and membrane p47 phox protein levels; and (4) induction of ROS production was abolished in p47 phoxϪ/Ϫ and gp91 phoxϪ/Ϫ macrophages. Finally, induction of NADPH oxidase by PPAR-␣ agonists resulted in the formation of oxidized LDL metabolites that exert PPAR-␣-independent proinflammatory and PPAR-␣-dependent decrease of lipopolysaccharide-induced inducible nitric oxide synthase expression in macrophages. These data identify a novel mechanism of autogeneration of endogenous PPAR-␣ ligands via stimulation of NADPH oxidase activity. Key Words: macrophages Ⅲ nuclear receptors Ⅲ NADPH oxidase Ⅲ reactive oxygen species Ⅲ inflammation P eroxisome proliferator-activated receptor ␣ (PPAR-␣) is a transcription factor belonging to the superfamily of ligandactivated nuclear receptors that heterodimerizes with the retinoid X receptor. In rodents, but not in humans, PPAR-␣ activation causes hepatomegaly attributable to parenchymal peroxisome proliferation, resulting in a marked increase in oxidative stress. 1 In humans, PPAR-␣ agonists are used for the treatment of dyslipidemia. PPAR-␣ regulates the expression of genes controlling lipid and lipoprotein metabolism and cholesterol and glucose homeostasis. PPAR-␣ activation results in decreased plasma triglyceride and small dense LDL levels and increased HDL. 2 PPAR-␣ also exerts antiinflammatory activities by transrepressing inflammatory signaling pathways. 2 PPAR-␣ is also expressed in vascular wall cells, including monocyte-derived macrophages, where it modulates cholesterol homeostasis. In macrophages, PPAR-␣ regulates the expression of the HDL receptor CLA-1/SR-B1 and the cholesterol/phospholipid transporter ABCA1. 3 Moreover, PPAR-␣ inhibits cholesterol esterification, resulting in an enhanced availability of free cholesterol for efflux through the ABCA1 pathway. 3 P...

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“…This suggests that activated PPARA, possibly phospo-PPARA, acts to promote SLC16A7 expression. SLC16A7 has not been identified as a target protein for peroxisome proliferation, but PPARs affect target genes by binding to a specific DR1 motif in a peroxisome proliferatorresponse element (PPRE) located upstream in the promoter region (Latruffe et al 2000). A brief assessment of the Slc16A7 gene identified such a DR1 sequence as well as sites for many stress-associated transcription factors such as: GATA; CREB; FKHD; HIF; and NFKB (Table 1), providing further support for the conclusion that the PPARA activation is upstream of SLC16A7 induction.…”

Section: Metabolic Stress In Embryosmentioning

confidence: 99%

Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-α (PPARA) cause peroxisome proliferation in preimplantation mouse embryos

Jansen

Cashman²,

Thompson³

et al. 2009

Reproduction

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Ex vivo two-cell mouse embryos deprived of glucose in vitro can develop to blastocysts by increasing their pyruvate consumption; however, zygotes when glucose-deprived cannot adapt this metabolic profile and degenerate as morulae. Prior to their death, these glucose-deprived morulae exhibit upregulation of the H C -monocarboxylate co-transporter SLC16A7 and catalase, which partly co-localize in peroxisomes. SLC16A7 has been linked to redox shuttling for peroxisomal b-oxidation. Peroxisomal function is unclear during preimplantation development, but as a peroxisomal transporter in embryos, SLC16A7 may be involved and influenced by peroxisome proliferators such as peroxisome proliferator-activated receptor-a (PPARA). PCR confirmed Ppara mRNA expression in mouse embryos. Zygotes were cultured with or without glucose and with the PPARA-selective agonist WY14643 and the developing embryos assessed for expression of PPARA and phospho-PPARA in relation to the upregulation of SLC16A7 and catalase driven by glucose deprivation, indicative of peroxisomal proliferation. Reactive oxygen species (ROS) production and relationship to PPARA expression were also analysed. In glucose-deprived zygotes, ROS was elevated within 2 h, as were PPARA expression within 8 h and catalase and SLC16A7 after 12-24 h compared with glucose-supplied embryos. Inhibition of ROS production prevented this induction of PPARA and SLC16A7. Selective PPARA agonism with WY14643 also induced SLC16A7 and catalase expression in the presence of glucose. These data suggest that glucose-deprived cleavage stage embryos, although supplied with sufficient monocarboxylate-derived energy, undergo oxidative stress and exhibit elevated ROS, which in turn upregulates PPARA, catalase and SLC16A7 in a classical peroxisomal proliferation response.

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Regulation of the peroxisomal β-oxidation-dependent pathway by peroxisome proliferator-activated receptor α and kinases

Cited by 74 publications

References 42 publications

Possible Role of Fatty Acids in Milk as the Regulator of the Expression of Cytosolic Binding Proteins for Fatty Acids and Vitamin A through PPAR.ALPHA. in Developing Rats

Possible Role of Fatty Acids in Milk as the Regulator of the Expression of Cytosolic Binding Proteins for Fatty Acids and Vitamin A through PPAR.ALPHA. in Developing Rats

Peroxisome Proliferator–Activated Receptor α Induces NADPH Oxidase Activity in Macrophages, Leading to the Generation of LDL with PPAR-α Activation Properties

Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-α (PPARA) cause peroxisome proliferation in preimplantation mouse embryos

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