scholarly journals Differential Activation of Nuclear Receptors by Perfluorinated Fatty Acid Analogs and Natural Fatty Acids: A Comparison of Human, Mouse, and Rat Peroxisome Proliferator-Activated Receptor-α, -β, and -γ, Liver X Receptor-β, and Retinoid X Receptor-α

2006 ◽  
Vol 92 (2) ◽  
pp. 476-489 ◽  
Author(s):  
John P. Vanden Heuvel ◽  
Jerry T. Thompson ◽  
Steven R. Frame ◽  
Peter J. Gillies
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Nuclear Receptors ◽  
Liver X Receptor ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Differential Activation

scholarly journals Role of peroxisome proliferator-activated receptor-α on the synthesis of monounsaturated fatty acids in goat mammary epithelial cells

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Huibin Tian ◽  
Jun Luo ◽  
Hengbo Shi ◽  
Xiaoying Chen ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Mammary Epithelial Cells ◽  
Acid Synthesis ◽  
Mammary Epithelial ◽  
Mrna Abundance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Goat Mammary Epithelial Cells

Abstract A key member of the nuclear receptor superfamily is the peroxisome proliferator-activated receptor alpha (PPARA) isoform, which in nonruminants is closely associated with fatty acid oxidation. Whether PPARA plays a role in milk fatty acid synthesis in ruminants is unknown. The main objective of the present study was to use primary goat mammary epithelial cells (GMEC) to activate PPARA via the agonist WY-14643 (WY) or to silence it via transfection of small-interfering RNA (siRNA). Three copies of the peroxisome proliferator-activated receptor response element (PPRE) contained in a luciferase reporter vector were transfected into GMEC followed by incubation with WY at 0, 10, 20, 30, 50, or 100 µM. A dose of 50 µM WY was most effective at activating PPRE without influencing PPARA mRNA abundance. Transfecting siRNA targeting PPARA decreased its mRNA abundance to 20% and protein level to 50% of basal levels. Use of WY upregulated FASN, SCD1, ACSL1, DGAT1, FABP4, and CD36 (1.1-, 1.5-, 2-, 1.4-, 1.5-, and 5-fold, respectively), but downregulated DGAT2 and PGC1A (−20% and −40%, respectively) abundance. In contrast, triacylglycerol concentration decreased and the content and desaturation index of C16:1 and C18:1 increased. Thus, activation of PPARA via WY appeared to channel fatty acids away from esterification. Knockdown of PPARA via siRNA downregulated ACACA, SCD1, AGPAT6, CD36, HSL, and SREBF1 (−43%, −67%, −16%, −56%, −26%, and −29%, respectively), but upregulated ACSL1, DGAT2, FABP3, and PGC1A (2-, 1.4-, 1.3-, and 2.5-fold, respectively) mRNA abundance. A decrease in the content and desaturation index of C16:1 and C18:1 coupled with an increase in triacylglycerol content accompanied those effects at the mRNA level. Overall, data suggest that PPARA could promote the synthesis of MUFA in GMEC through its effects on mRNA abundance of genes related to fatty acid synthesis, oxidation, transport, and triacylglycerol synthesis.

scholarly journals Peroxisome-proliferator-activated receptor-α (PPARα) deficiency leads to dysregulation of hepatic lipid and carbohydrate metabolism by fatty acids and insulin

2002 ◽  
Vol 364 (2) ◽  
pp. 361-368 ◽  
Author(s):  
Mary C. SUGDEN ◽  
Karen BULMER ◽  
Geoffrey F. GIBBONS ◽  
Brian L. KNIGHT ◽  
Mark J. HOLNESS
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Carbohydrate Metabolism ◽  
Plasma Insulin ◽  
Hepatic Glycogen ◽  
Peroxisome Proliferator ◽  
Hepatic Lipogenesis ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Lipid

The aim of the present study was to determine whether peroxisome-proliferator-activated receptor-α (PPARα) deficiency disrupts the normal regulation of triacylglycerol (TAG) accumulation, hepatic lipogenesis and glycogenesis by fatty acids and insulin using PPARα-null mice. In wild-type mice, hepatic TAG concentrations increased (P<0.01) with fasting (24h), with substantial reversal after refeeding (6h). Hepatic TAG levels in fed PPARα-null mice were 2.4-fold higher than in the wild-type (P<0.05), increased with fasting, but remained elevated after refeeding. PPARα deficiency also impaired hepatic glycogen repletion (P<0.001), despite normal insulin and glucose levels after refeeding. Higher levels of plasma insulin were required to support similar levels of hepatic lipogenesis de novo (3H2O incorporation) in the PPARα-null mice compared with the wild-type. This difference was reflected by corresponding changes in the relationship between plasma insulin and the mRNA expression of the lipogenic transcription factor sterol-regulatory-element-binding protein-1c, and that of one of its known targets, fatty acid synthase. In wild-type mice, hepatic pyruvate dehydrogenase kinase (PDK) 4 protein expression (a downstream marker of altered fatty acid catabolism) increased (P<0.01) in response to fasting, with suppression (P<0.001) by refeeding. Although PDK4 up-regulation after fasting was halved by PPARα deficiency, PDK4 suppression after refeeding was attenuated. In summary, PPARα deficiency leads to accumulation of hepatic TAG and elicits dysregulation of hepatic lipid and carbohydrate metabolism, emphasizing the importance of precise control of lipid oxidation for hepatic fuel homoeostasis.

scholarly journals Effects of fatty acids on gene expression: role of peroxisome proliferator-activated receptor α, liver X receptor α and sterol regulatory element-binding protein-1c

2002 ◽  
Vol 61 (3) ◽  
pp. 371-374 ◽  
Author(s):  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Dietary Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver X Receptor Α ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Dietary fatty acids have numerous effects on cellular function, many of which are achieved by altering the expression of genes. The present paper reviews recent data on the mechanisms by which fatty acids influence DNA transcription, and focus specifically on the importance of three transcription factors: peroxisome proliferator-activated receptor α; liver X receptor α; sterol regulatory element-binding protein 1c. These data indicate that fatty acids induce or inhibit the mRNA expression of a variety of different genes by acting both as agonists and as antagonists for nuclear hormone receptors.

scholarly journals Hepatic Peroxisomal Fatty Acid β-Oxidation Is Regulated by Liver X Receptor α

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5380-5387 ◽  
Author(s):  
Tonghuan Hu ◽  
Patricia Foxworthy ◽  
Angela Siesky ◽  
James V. Ficorilli ◽  
Hong Gao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Liver Steatosis ◽  
Liver X Receptor ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acids ◽  
Lxr Agonists ◽  
Long Chain ◽  
Chain Fatty Acids

Peroxisomes are the exclusive site for the β-oxidation of very-long-chain fatty acids of more than 20 carbons in length (VLCFAs). Although the bulk of dietary long-chain fatty acids are oxidized in the mitochondria, VLCFAs cannot be catabolized in mitochondria and must be shortened first by peroxisomal β-oxidation. The regulation of peroxisomal, mitochondrial, and microsomal fatty acid oxidation systems in liver is mediated principally by peroxisome proliferator-activated receptor α (PPARα). In this study we provide evidence that the liver X receptor (LXR) regulates the expression of the genetic program for peroxisomal β-oxidation in liver. The genes encoding the three enzymes of the classic peroxisomal β-oxidation cycle, acyl-coenzyme A (acyl-CoA) oxidase, enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, are activated by the LXR ligand, T0901317. Accordingly, administration of T0901317 in mice promoted a dose-dependent and greater than 2-fold increase in the rate of peroxisomal β-oxidation in the liver. The LXR effect is independent of PPARα, because T0901317-induced peroxisomal β-oxidation in the liver of PPARα-null mice. Interestingly, T0901317-induced peroxisomal β-oxidation is dependent on the LXRα isoform, but not the LXRβ isoform. We propose that induction of peroxisomal β-oxidation by LXR agonists may serve as a counterregulatory mechanism for responding to the hypertriglyceridemia and liver steatosis that is promoted by potent LXR agonists in vivo; however, additional studies are warranted.

scholarly journals Induction of Cardiac Angptl4 by Dietary Fatty Acids Is Mediated by Peroxisome Proliferator-Activated Receptor β/δ and Protects Against Fatty Acid–Induced Oxidative Stress

2010 ◽  
Vol 106 (11) ◽  
pp. 1712-1721 ◽  
Author(s):  
Anastasia Georgiadi ◽  
Laeticia Lichtenstein ◽  
Tatjana Degenhardt ◽  
Mark V. Boekschoten ◽  
Marc van Bilsen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Dietary Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

295. Peroxisome proliferator activated receptor-alpha is involved in H+-monocarboxylate transporter 2 and catalase protein expression in cultured preimplantation mouse embryos

2005 ◽  
Vol 17 (9) ◽  
pp. 125
Author(s):  
S. Jansen ◽  
M. Pantaleon ◽  
P. L. Kaye
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Mouse Embryos ◽  
Preimplantation Development ◽  
Monocarboxylate Transporter ◽  
Metabolic Inhibitors ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Beta Oxidation ◽  
Peroxisome Proliferator Activated Receptor

Cleavage stage embryos consume pyruvate before switching to glucose as the major energy substrate for blastocyst formation. This switch is conditional, because freshly collected two-cell embryos form blastocysts without glucose by increasing pyruvate consumption. Zygotes cultured without glucose cannot adapt in this way and degenerate, but paradoxically demonstrate upregulation of the H+-monocarboxylate transporter protein, MCT2, in morulae. MCT2 is a high affinity transporter implicated in redox shuttling for peroxisomal beta-oxidation of fatty acids.3 Fatty acids may provide energy for embryos2 but peroxisomal beta-oxidation has not been explored in preimplantation development. Rat oocytes possess a primitive peroxisomal system.1 The possibility therefore exists that MCT2 may also be linked to fatty acid metabolism in embryos. Peroxisome proliferator activated receptor (PPAR)-alpha is a transcriptional regulator of fatty acid transport and beta-oxidation, and controls expression of catalase, a major peroxisomal enzyme. This investigation explores the role of PPAR-α in the glucose-driven control of MCT2 expression in mouse embryos. Zygotes (18 h post-hCG) were cultured in KSOM in the presence or absence of glucose, or KSOM with selective agonists of PPAR-α, fenofibrate and WY 14643. Expression of MCT2 and catalase was analysed by confocal laser scanning immunohistochemistry and western blot. Results confirm the presence of catalase throughout preimplantation development. With glucose, cytoplasmic immunoreactivity for catalase was punctate and diffuse, while MCT2 was localised to apical membranes of outer blastomeres in morulae. Without glucose, catalase and MCT2 expression were increased with notable localisation of catalase to nuclei. This response was reflected in morulae cultured in the presence of glucose and PPAR-α agonists. These data suggest that PPAR-α plays a role in controlling catalase and MCT2 expression in embryos, and that conditions in the absence of glucose are more conducive for PPAR-α activation. (1)Figueroa C, Kawada ME, Veliz LP, Hidalgo U, Barros C, Gonzalez S and Santos MJ (2000) Peroxisomal proteins in rat gametes. Cell Biochem Biophys 32, 259–268.(2)Hewitson LC, Martin KL and Leese HJ (1996) Effects of metabolic inhibitors on mouse preimplantation embryo development and the energy metabolism of isolated inner cell masses. Mol Reprod Dev 43, 323–330.(3)McClelland GB, Khanna S, Gonzalez GF, Butz CE and Brooks GA (2003) Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system? Biochem Biophys Res Commun 304, 130–135.

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