Maternal diets enriched in olive oil regulate lipid metabolism and levels of PPARs and their coactivators in the fetal liver in a rat model of gestational diabetes mellitus

Fornes, Daiana; Ribot, Dalmiro Gomez; Heinecke, Florencia; Roberti, Sabrina Lorena; Capobianco, Evangelina; Jawerbaum, Alicia

doi:10.1016/j.jnutbio.2019.108334

Cited by 12 publications

(7 citation statements)

References 46 publications

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“…Essential coregulators are proteins deemed critical for the survival of the offspring, and their absence results in embryonic lethality: cAMP-response element-binding protein (CBP); PPAR-interacting protein/activating signal cointegrator 2 (PRIP/ASC2); PPAR-binding protein/mediator complex subunit 1 (PBP/Med1); mediator complex subunit 25 (Med25) [131][132][133]. Non-essential coregulators are proteins with such critical functional responsibilities that they are usually represented by more than one isoform-steroid receptor coactivators (SRCs) [131,132,134], Asp-Glu-Ala-Asp (DEAD)-box helicases [135][136][137], sirtuins (SIRT) [96,97], PPARγ coactivators (PGCs) [138][139][140][141]-and the loss of one isoform is compensated by others. Repressors that bind to the nuclear receptor PPARα in the absence of/or independent of ligands prevent it from binding to the peroxisomal proliferator response elements (PPRE) of the target genes as nuclear corepressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone (SMRT) [96] (Figure 7A).…”

Section: Pparα and Coregulatorsmentioning

confidence: 99%

Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

Tahri-Joutey

Andreoletti

Surapureddi

et al. 2021

IJMS

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In mammalian cells, two cellular organelles, mitochondria and peroxisomes, share the ability to degrade fatty acid chains. Although each organelle harbors its own fatty acid β-oxidation pathway, a distinct mitochondrial system feeds the oxidative phosphorylation pathway for ATP synthesis. At the same time, the peroxisomal β-oxidation pathway participates in cellular thermogenesis. A scientific milestone in 1965 helped discover the hepatomegaly effect in rat liver by clofibrate, subsequently identified as a peroxisome proliferator in rodents and an activator of the peroxisomal fatty acid β-oxidation pathway. These peroxisome proliferators were later identified as activating ligands of Peroxisome Proliferator-Activated Receptor α (PPARα), cloned in 1990. The ligand-activated heterodimer PPARα/RXRα recognizes a DNA sequence, called PPRE (Peroxisome Proliferator Response Element), corresponding to two half-consensus hexanucleotide motifs, AGGTCA, separated by one nucleotide. Accordingly, the assembled complex containing PPRE/PPARα/RXRα/ligands/Coregulators controls the expression of the genes involved in liver peroxisomal fatty acid β-oxidation. This review mobilizes a considerable number of findings that discuss miscellaneous axes, covering the detailed expression pattern of PPARα in species and tissues, the lessons from several PPARα KO mouse models and the modulation of PPARα function by dietary micronutrients.

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Section: Pparα and Coregulatorsmentioning

confidence: 99%

Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

Tahri-Joutey

Andreoletti

Surapureddi

et al. 2021

IJMS

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“…For instance, Sun et al (2019) showed that pomegranate ellagic polyphenols activated PPARα-TRB3-AKT2p-FOXO1-GLUT2 signaling (associated with insulin sensitivity) in a dose-dependent manner. Fornes et al (2020) reported that a diet supplemented with 6% olive oil prevented the increase in PPARγ and PPARδ levels in the male fetuses of pregnant rats. On the other hand, Capobianco reported that a maternal diet supplemented with polyunsaturated fatty acids attenuated mTOR signaling, preventing fetal overgrowth (Capobianco et al, 2018b).…”

Section: Ffis Increase Insulin Secretion and Potentiate Insulin Signalingmentioning

confidence: 99%

Functional food ingredients for control of gestational diabetes mellitus: a review

Lin

Zhang

et al. 2022

Food Sci. Technol

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Gestational diabetes mellitus (GDM) is highly prevalent worldwide, with an estimated 10-15% percent of pregnancies affected. Increasing evidence indicates that functional food ingredients (FFIs) may help relieve GDM via multiple mechanisms, such as eliminating free radicals, downregulating inflammation, promoting insulin secretion and signaling, targeting hepatic gluconeogenesis and glycogen storage metabolism, and regulating the intestinal microflora. In this article, the effects of functional food ingredients on GDM and the possible underlying mechanisms of action are reviewed. This review provides reference information that can be useful for the development of novel functional supplements for the control of GDM.

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“…This was not confirmed by the RTqPCR data (see the limitation session). Similarly, perilipin 2 (PLIN2), upregulated by both the PPARδ and PPARγ agonists, is a known PPAR target in monogastrics (71), though it is of note that while in monogastrics PLIN2 is identified as a target of PPARα, studies in goats found its expression to be responsive to rosiglitazone, the same PPARγ agonist used in this study (72). VLDLR, the gene encoding the VLDL receptor, was upregulated by the PPARα agonist, and substantial evidence exists indicating it as a target gene of PPARδ (73) and PPARα (74), through which it contributes to lowering serum TAG in mice.…”

Section: Most Of Confirmed Ppar Targets Are Involved In Lipid Metabolismmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows

et al. 2022

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Metabolic challenges experienced by dairy cows during the transition between pregnancy and lactation (also known as peripartum), are of considerable interest from a nutrigenomic perspective. The mobilization of large amounts of non-esterified fatty acids (NEFA) leads to an increase in NEFA uptake in the liver, the excess of which can cause hepatic accumulation of lipids and ultimately fatty liver. Interestingly, peripartum NEFA activate the Peroxisome Proliferator-activated Receptor (PPAR), a transcriptional regulator with known nutrigenomic properties. The study of PPAR activation in the liver of periparturient dairy cows is thus crucial; however, current in vitro models of the bovine liver are inadequate, and the isolation of primary hepatocytes is time consuming, resource intensive, and prone to errors, with the resulting cells losing characteristic phenotypical traits within hours. The objective of the current study was to evaluate the use of precision-cut liver slices (PCLS) from liver biopsies as a model for PPAR activation in periparturient dairy cows. Three primiparous Jersey cows were enrolled in the experiment, and PCLS from each were prepared prepartum (−8.0 ± 3.6 DIM) and postpartum (+7.7± 1.2 DIM) and treated independently with a variety of PPAR agonists and antagonists: the PPARα agonist WY-14643 and antagonist GW-6471; the PPARδ agonist GW-50156 and antagonist GSK-3787; and the PPARγ agonist rosiglitazone and antagonist GW-9662. Gene expression was assayed through RT-qPCR and RNAseq, and intracellular triacylglycerol (TAG) concentration was measured. PCLS obtained from postpartum cows and treated with a PPARγ agonist displayed upregulation of ACADVL and LIPC while those treated with PPARδ agonist had increased expression of LIPC, PPARD, and PDK4. In PCLS from prepartum cows, transcription of LIPC was increased by all PPAR agonists and NEFA. TAG concentration tended to be larger in tissue slices treated with PPARδ agonist compared to CTR. Use of PPAR isotype-specific antagonists in PCLS cultivated in autologous blood serum failed to decrease expression of PPAR targets, except for PDK4, which was confirmed to be a PPARδ target. Transcriptome sequencing revealed considerable differences in response to PPAR agonists at a false discovery rate-adjusted p-value of 0.2, with the most notable effects exerted by the PPARδ and PPARγ agonists. Differentially expressed genes were mainly related to pathways involved with lipid metabolism and the immune response. Among differentially expressed genes, a subset of 91 genes were identified as novel putative PPAR targets in the bovine liver, by cross-referencing our results with a publicly available dataset of predicted PPAR target genes, and supplementing our findings with prior literature. Our results provide important insights on the use of PCLS as a model for assaying PPAR activation in the periparturient dairy cow.

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Maternal diets enriched in olive oil regulate lipid metabolism and levels of PPARs and their coactivators in the fetal liver in a rat model of gestational diabetes mellitus

Cited by 12 publications

References 46 publications

Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

Functional food ingredients for control of gestational diabetes mellitus: a review

Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows

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