Novel aspects of PPARα-mediated regulation of lipid and xenobiotic metabolism revealed through a nutrigenomic study

Martin, Pascal G.P.; Guillou, Hervé; Lasserre, Frédèric; Déjean, Sébastien; Lan, Annaïg; Pascussi, Jean‐Marc; SanCristobal, Magali; Legrand, Philippe; Besse, Philippe; Pineau, Thierry

doi:10.1002/hep.21510

Cited by 114 publications

(111 citation statements)

References 39 publications

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“…Interestingly, in our porcine model, a lower or higher than normal birth weight was found to affect the gene expression of FABP3, FABP4, PPARA, and PPARG2, which are likely to be linked to changes in lipid metabolism, although we have not measured this directly in the current study (Binas et al 1999, Norris et al 2003, Boord et al 2004, Martin et al 2007. Further work should include assessment of whether the changes in mRNA expression are translated to protein.…”

Section: Discussionmentioning

confidence: 67%

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs

Williams¹,

Marten²,

Wilson³

et al. 2009

Reproduction

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Epidemiological studies suggest that low-birth weight infants show poor neonatal growth and increased susceptibility to metabolic syndrome, in particular, obesity and diabetes. Adipose tissue development is regulated by many genes, including members of the peroxisome proliferator-activated receptor (PPAR) and the fatty acid-binding protein (FABP) families. The aim of this study was to determine the influence of birth weight on key adipose and skeletal muscle tissue regulating genes. Piglets from 11 litters were ranked according to birth weight and 3 from each litter assigned to small, normal, or large-birth weight groups. Tissue samples were collected on day 7 or 14. Plasma metabolite concentrations and the expression of PPARG2, PPARA, FABP3, and FABP4 genes were determined in subcutaneous adipose tissue and skeletal muscle. Adipocyte number and area were determined histologically. Expression of FABP3 and 4 was significantly reduced in small and large, compared with normal, piglets in adipose tissue on day 7 and in skeletal muscle on day 14. On day 7, PPARA and PPARG2 were significantly reduced in adipose tissue from small and large piglets. Adipose tissue from small piglets contained more adipocytes than normal or large piglets. Birth weight had no effect on adipose tissue and skeletal muscle lipid content. Low-birth weight is associated with tissue-specific and time-dependent effects on lipid-regulating genes as well as morphological changes in adipose tissue. It remains to be seen whether these developmental changes alter an individual's susceptibility to metabolic syndrome.

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Section: Discussionmentioning

confidence: 67%

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs

Williams¹,

Marten²,

Wilson³

et al. 2009

Reproduction

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“…Organ-specific transcriptomic profiles were obtained using a nuclear receptors-dedicated cDNA macroarray (INRArray 01.4) previously developed and validated [38,39]; full list of 320 cDNA probes available at http://www.inra.fr/internet/Centres /toulouse/pharmacologie/pharmacomoleculaire/technologie /inrarray-01-4.html. Total hepatic RNA was extracted with TRIzol reagent (Invitrogen, Cergy Pontoise, France) according to the manufacturer's protocol.…”

Section: Transcriptomic Analysesmentioning

confidence: 99%

“…RNA integrity was controlled on a Bioanalyzer 2100 (Agilent, Massy, France) and assayed at 260 nm on a Lambda 650 spectrophotometer (Perkin Elmer, Toulouse, France). RNA labelling and hybridization to INRArray 01.4 were performed as previously described [39]. The raw and processed data are available in the Gene Expression Omnibus (GEO) database [40] under the accession number GSE14920.…”

Section: Transcriptomic Analysesmentioning

confidence: 99%

Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): A novel signalling pathway sensitive to phthalates

Eveillard¹,

Mselli-Lakhal²,

Mogha³

et al. 2009

Biochemical Pharmacology

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To cite this version:Alexandre Eveillard, Laïla Mselli-Lakhal, Ariane Mogha, Frédéric Lasserre, Arnaud Polizzi, et al.. Di-(2-ethylhexyl)-phthalate (DEHP) activates the Constitutive Androstane Receptor (CAR): a novel signalling pathway sensitive to phthalates. Biochemical Pharmacology, Elsevier, 2009, 77 (11) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 This finding demonstrates that CAR also represents a transcriptional regulator sensitive to phthalates. CAR-mediated effects of DEHP provide a new rationale for most endpoints of phthalates toxicity described previously, including endocrine disruption, hepatocarcinogenesis and the metabolic syndrome.

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“…The most noticeable effect of PUFA is generally recognized as suppression of lipogenesis, which is primarily attributable to down-regulation of sterol regulatory element-binding protein-1c (SREBP-1c) (Kim et al 1999;Mater et al 1999;Sekiya et al 2003;Tanaka et al 2010), the master transcription factor for genes involved in FA and TG synthesis (Horton et al 2002). PUFA are also known to stimulate FA degradation by activating peroxisome proliferatoractivated receptor α (PPARα) (Ren et al 1997;Martin et al 2007), which is a ligand-dependent nuclear receptor that regulates the transcription of genes involved in FA β-oxidation (Aoyama et al 1998;Kamijo et al 2007). These two effects are proposed as the main mechanisms responsible for the liver TG-lowering action of PUFA.…”

Section: Introductionmentioning

confidence: 99%

“…However, previous studies have some limitations in their experimental conditions. For example, to induce a PUFA-deficient condition, the previous studies generally used two types of PUFA-deficient diets: a fat-free diet or a 4-5% (w/w) hydrogenated coconut oil (HCO)-containing diet (Martin et al 2007;Ducheix et al 2013). However, these diets contain very small amounts of long-chain FA (< 1.5% in diet, w/w) compared with standard diets (4-7% in diet, w/w).…”

Section: Introductionmentioning

confidence: 99%

Decreased Fatty Acid <i>β</i>-Oxidation Is the Main Cause of Fatty Liver Induced by Polyunsaturated Fatty Acid Deficiency in Mice

Nakajima

Yang

et al. 2017

Tohoku J. Exp. Med.

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Insufficient intake of polyunsaturated fatty acids (PUFA) causes fatty liver. The mechanism responsible is primarily related to increased lipogenesis and decreased FA degradation based on rodent studies. However, these studies were limited by the fact that the typical PUFA-deficient diets contained insufficient amounts of long-chain FA, the PUFA-containing diets were primarily composed of n-3 PUFA-enriched oil, and the intake of PUFA was excessive compared with the physiological requirement. To address these issues, mice were fed a PUFA-deficient diet containing long-chain FA at a standard fed level and then were orally fed a n-3/n-6-balanced PUFA-containing oil [PUFA (+)] or a PUFA-deficient oil [PUFA (−)] at physiological relevant levels (0.1 mL/mouse/2d). We compared these groups and examined whether fatty liver in PUFA deficiency was attributable to both the effects of increased lipogenesis and decreased FA catabolism. Compared with the PUFA (+) group, the PUFA (−) group showed increases in liver triglyceride and serum FA content. Hepatic gene expression of several mitochondrial β-oxidation enzymes, the serum 3-hydroxybutyrate level, and DNA-binding ability of peroxisome proliferator-activated receptor α (PPARα) were increased in the PUFA (+) group, whereas these adaptive responses were significantly attenuated in the PUFA (−) group. The hepatic expression of typical lipogenesis genes did not differ between the groups. Therefore, fatty liver in PUFA deficiency is attributable to suppression of the FA-degrading system probably from decreased PPARα adaptive responsiveness, and PUFA may be an essential factor for PPARα functioning. This finding is helpful for managing clinical situations having a risk of PUFA deficiency.

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Novel aspects of PPARα-mediated regulation of lipid and xenobiotic metabolism revealed through a nutrigenomic study

Cited by 114 publications

References 39 publications

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs

Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): A novel signalling pathway sensitive to phthalates

Decreased Fatty Acid <i>β</i>-Oxidation Is the Main Cause of Fatty Liver Induced by Polyunsaturated Fatty Acid Deficiency in Mice

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