Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors

Dreyer, Christine; Krey, Grigorios; Keller, H. J.; Givel, Françoise; Helftenbein, Gerd; Wahli, Walter

doi:10.1016/0092-8674(92)90031-7

Cited by 1,279 publications

(791 citation statements)

References 34 publications

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“…Drugs of the fibrate class are used clinically to reduce serum triglyceride and cholesterol levels and have been shown to activate the PPARs (11,(21)(22)(23)(24). Recently, a novel class of trisubstituted ureido fibrate analogues was synthesized which displayed increased potency in rodent models of hyperlipidemia (D. Winegar, and S.S.S., unpublished data).…”

Section: Resultsmentioning

confidence: 99%

“…To generate bacterial expression plasmids for the ligand binding domains of the PPAR subtypes, cDNAs encoding the hinge and ligand binding domains of hPPAR␣ (amino acids 167-468) (20), mPPAR␣ (amino acids 167-468) (5), xPPAR␣ (amino acids 174-474) (11), and xPPAR␥ (amino acids 178-477) (11) were removed from the corresponding pSG-GAL4-PPAR chimeric receptor expression plasmids by cutting with KpnI and BamHI and inserted in frame into a pGEX-2T plasmid (Pharmacia) that had been modified to include KpnI and BamHI sites in the polylinker region. GST-PPAR fusion proteins or glutathione Stransferase (GST) alone as a control were expressed in BL21(DE3)plysS cells and extracts prepared by freeze-thawing the cells in bacterial lysis buffer (10 mM Tris, pH 8.0/250 mM KCl/1 mM DTT/1% Triton X-100) followed by centrifugation at 40,000 ϫ g for 30 min.…”

Section: Chemicals 2-(4-mentioning

confidence: 99%

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Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ

Kliewer

Sundseth

Jones

et al. 1997

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

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Peroxisome proliferator-activated receptors (PPARs) ␣ and ␥ are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds including fatty acids, eicosanoids, and hypolipidemic drugs such as fibrates and thiazolidinediones. While thiazolidinediones and 15-deoxy-⌬ 12,14 -prostaglandin J 2 have been shown to bind to PPAR␥, it has remained unclear whether other activators mediate their effects through direct interactions with the PPARs or via indirect mechanisms. Here, we describe a novel fibrate, designated GW2331, that is a highaffinity ligand for both PPAR␣ and PPAR␥. Using GW2331 as a radioligand in competition binding assays, we show that certain mono-and polyunsaturated fatty acids bind directly to PPAR␣ and PPAR␥ at physiological concentrations, and that the eicosanoids 8(S)-hydroxyeicosatetraenoic acid and 15-deoxy-⌬ 12,14 -prostaglandin J 2 can function as subtypeselective ligands for PPAR␣ and PPAR␥, respectively. These data provide evidence that PPARs serve as physiological sensors of lipid levels and suggest a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Chemicals 2-(4-mentioning

confidence: 99%

Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ

Kliewer

Sundseth

Jones

et al. 1997

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

Self Cite

1,960

1,281

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“…The fact that OEA resembles lipid compounds that activate the PPAR family of nuclear receptors, such as non-esterified fatty acids [35], prompted us to explore the possibility that this molecule might target one of these ligand-activated transcription factors. PPAR receptors, first identified in 1992 [36], are a family of ligand-activated transcription factors that comprises three known isoforms, PPAR-a, PPAR-d (also called PPAR-b) and PPAR-g. PPAR-a receptors, the molecular target of the fibrate class of antihyperlipidemic drugs, induce a variety of transcriptional changes that result in increased fatty-acid catabolism, reduced blood lipid levels and lowered body-weight gain (reviewed in [35,37]). They also regulate inflammation through transcriptional and non-transcriptional actions [38].…”

Section: Oea Is An Endogenous Ppar-a a Agonistmentioning

confidence: 99%

Regulation of food intake by oleoylethanolamide

Verme

Gaetani

et al. 2005

CMLS, Cell. Mol. Life Sci.

155

130

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Abstract. Oleoylethanolamide (OEA), the naturally occurring amide of ethanolamine and oleic acid, is an endogenous lipid that modulates feeding, body weight and lipid metabolism by binding with high affinity to the ligand-activated transcription factor, peroxisome proliferator-activated receptor-alpha (PPAR-a). In the CMLS, Cell. Mol. Life Sci. 62 (2005) 708 -716 1420-682X/05/060708-09 DOI 10.1007/s00018-004-4494-0 © Birkhäuser Verlag, Basel, 2005 CMLS Cellular and Molecular Life Sciencespresent article, we describe the biochemical pathways responsible for the initiation and termination of OEA signaling, and outline the pharmacological properties of this compound in relation to its ability to activate PPARa. Finally, we discuss the possible role of OEA as a peripheral satiety hormone.

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“…PPARs compose a subgroup of three receptors, belonging to the nuclear hormone receptor family, and acting as lipid sensors to modulate gene expression [144,145]. They are implicated in both major metabolic regulations and processes controlling cellular fate [146].…”

Section: Role Of the Pparg In Watmentioning

confidence: 99%

Fat poetry: a kingdom for PPARγ

2007

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Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor g (PPARg), which is a fatty acid-and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARg agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARg in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARg modulators.

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Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors

Cited by 1,279 publications

References 34 publications

Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ

Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ

Regulation of food intake by oleoylethanolamide

Fat poetry: a kingdom for PPARγ

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