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Debrecen, Hungary

Ruhl R.,Paprika Bioanalytics BT | Ruhl R.,Hungarian Academy of Sciences | Landrier J.F.,French National Institute for Agricultural Research | Landrier J.F.,French Institute of Health and Medical Research | Landrier J.F.,Aix - Marseille University
Molecular Nutrition and Food Research | Year: 2016

Adiponectin is an adipokine mainly secreted by adipocytes that presents antidiabetic, anti-inflammatory, and antiatherogenic functions. Therefore, modulation of adiponectin expression represents a promising target for prevention or treatment of several diseases including insulin resistance and type II diabetes. Pharmacological agents such as the nuclear hormone receptor synthetic agonists like peroxisome proliferator activated receptor γ agonists are of particular interest in therapeutic strategies due to their ability to increase the plasma adiponectin concentration. Nutritional approaches are also of particular interest, especially in primary prevention, since some active compounds of our diet (notably vitamins, carotenoids, or other essential nutrients) are direct or indirect lipid-activators of nuclear hormone receptors and are modifiers of adiponectin expression and secretion. The aim of the present review is to summarize current knowledge about the nutritional regulation of adiponectin by derivatives of active compounds naturally present in the diet acting as indirect or direct activators of nuclear hormone receptors. The aim of the present review is to summarize current knowledge about the nutritional regulation of adiponectin by derivatives of actives compounds naturally present in the diet acting as indirect or direct activators of nuclear hormone receptors such as VDR, RAR, RXR, PPARγ, or PXR. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ruhl R.,Debrecen University | Krzyzosiak A.,French Institute of Health and Medical Research | Krzyzosiak A.,University of Strasbourg | Krzyzosiak A.,Medical Research Council MRC Laboratory of Molecular Biology | And 19 more authors.
PLoS Genetics | Year: 2015

The retinoid X receptors (RXRs) are ligand-activated transcription factors which heterodimerize with a number of nuclear hormone receptors, thereby controlling a variety of (patho)-physiological processes. Although synthetic RXR ligands are developed for the treatment of various diseases, endogenous ligand(s) for these receptors have not been conclusively identified. We show here that mice lacking cellular retinol binding protein (Rbp1-/-) display memory deficits reflecting compromised RXR signaling. Using HPLC-MS and chemical synthesis we identified in Rbp1-/- mice reduced levels of 9-cis-13,14-dihydroretinoic acid (9CDHRA), which acts as an RXR ligand since it binds and transactivates RXR in various assays. 9CDHRA rescues the Rbp1-/- phenotype similarly to a synthetic RXR ligand and displays similar transcriptional activity in cultured human dendritic cells. High endogenous levels of 9CDHRA in mice indicate physiological relevance of these data and that 9CDHRA acts as an endogenous RXR ligand. © 2015 Rühl et al.

Kiss B.,Debrecen University | Szanto M.,Debrecen University | Szanto M.,Hungarian Academy of Sciences | Szklenar M.,Paprika Bioanalytics BT | And 11 more authors.
Molecular Medicine Reports | Year: 2015

Poly(ADP-ribose) polymerase (PARP)-1 is a pro-inflammatory protein. The inhibition of PARP-1 reduces the activity of numerous pro-inflammatory transcription factors, which results in the reduced production of pro-inflam-matory cytokines, chemokines, matrix metalloproteinases and inducible nitric oxide synthase, culminating in reduced inflam-mation of the skin and other organs. The aim of the present study was to investigate the effects of the deletion of PARP-1 expression on polyunsaturated fatty acids (PUFA), and PUFA metabolite composition, in mice under control conditions or undergoing an oxazolone (OXA)-induced contact hypersensitivity reaction (CHS). CHS was elicited using OXA in both the PARP-1+/+ and PARP-1-/- mice, and the concentration of PUFAs and PUFA metabolites in the diseased skin were assessed using lipidomics experiments. The levels of docosa-hexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were shown to be increased in the PARP-1-/- mice, as compared with the control, unsensitized PARP-1+/+ mice. In addition, higher expression levels of fatty acid binding protein 7 (FABP7) were detected in the PARP-1-/- mice. FABP7 is considered to be a specific carrier of DHA and EPA. Furthermore, the levels of the metabolites of DHA and EPA (considered mainly as anti-inflammatory or pro-resolving factors) were higher, as compared with the metabolites of arachidonic acid (considered mainly pro-inflammatory), both in the unsensitized control and OXA-sensitized PARP-1-/- mice. The results of the present study suggest that the genetic deletion of PARP-1 may affect the PUFA-homeostasis of the skin, resulting in an anti-inflammatory milieu, including increased DHA and EPA levels, and DHA and EPA metabolite levels. This may be an important component of the anti-inflammatory action of PARP-1 inhibition.

De Lera A.R.,University of Vigo | Krezel W.,University of Strasbourg | Ruhl R.,Paprika Bioanalytics BT | Ruhl R.,Hungarian Academy of Sciences
ChemMedChem | Year: 2016

9-cis-Retinoic acid was identified and claimed to be the endogenous ligand of the retinoid X receptors (RXRs) in 1992. Since then, the endogenous presence of this compound has never been rigorously confirmed. Instead, concerns have been raised by other groups that have reported that 9-cis-retinoic acid is undetectable or that its presence occurs at very low levels. Furthermore, these low levels could not satisfactorily explain the physiological activation of RXR. Alternative ligands, among them various lipids, have also been identified, but also did not fulfill criteria for rigorous endogenous relevance, and their consideration as bona fide endogenous mammalian RXR ligand has likewise been questioned. Recently, novel studies claim that the saturated analogue 9-cis-13,14-dihydroretinoic acid functions as an endogenous physiologically relevant mammalian RXR ligand. Receptive to feedback: 9-cis-13,14-Dihydroretinoic acid may be the first endogenous physiologically relevant mammalian retinoid X receptor (RXR) ligand. It binds to and activates RXR, displays biological activities similar to those of synthetic RXR agonists, and coordinates the transcriptional activities of several nuclear receptor signaling pathways, possibly through the corresponding permissive heterodimers. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zein Elabdeen H.R.,University of Bergen | Mustafa M.,University of Bergen | Szklenar M.,Paprika Bioanalytics BT | Ruhl R.,Paprika Bioanalytics BT | And 3 more authors.
PLoS ONE | Year: 2013

Aggressive periodontitis (AgP) is a rapidly progressing type of periodontal disease in otherwise healthy individuals which causes destruction of the supporting tissues of the teeth. The disease is initiated by pathogenic bacteria in the dental biofilm, and the severity of inflammation and attachment loss varies with the host response. Recently, there has been an increased interest in determining the role of lipid mediators in inflammatory events and the concept of pro-inflammatory and pro-resolution lipid mediators has been brought into focus also in periodontal disease. The present study aimed to determine the profile of omega-3 or n3- as well as omega-6 or n6- polyunsaturated fatty acids (PUFAs) and PUFA-metabolites of linoleic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in gingival crevicular fluid (GCF), saliva and serum in AgP patients and healthy controls. In total, 60 selected n3- and n6-PUFAs and various PUFA metabolites were measured using high performance liquid chromatography-tandem electrospray ionisation mass spectrometry (HPLC-ESI-MS-MS). Of these, 51 could be quantified in this study. The concentrations of the majority were low in saliva samples compared with serum and GCF, but were mainly higher in AgP patients compared with healthy controls in all three kinds of sample. Ratios of n3- to n6-PUFAs (DHA + EPA)/AA were significantly lower in the GCF of AgP patients than in the healthy controls. Furthermore, various ratios of the direct precursors of the pro-resolution lipid mediators (precursors of resolvins and protectins) were calculated against the precursors of mainly pro-inflammatory lipid mediators. These ratios were mainly lower in GCF and saliva of AgP patients, compared with healthy controls, but only reached significance in GCF (P<0.05). To conclude, the ratios of precursors of pro-resolution/pro-inflammatory lipid mediators seem to be more relevant for describing the disease status of AgP than the concentration of specific lipid mediators. © 2013 Elabdeen et al.

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