Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND & AIMS: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. RESULTS: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. CONCLUSIONS: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.
ISSN: 0168-8278

inserm-00872314
http://www.hal.inserm.fr/inserm-00872314
DOI : 10.1016/j.jhep.2013.01.006
PUBMED : 23333450

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Blake excursion was among the first recognized with directional and intensity behavior known mainly from marine sediment and Chinese loess. Age estimates for the directional shifts in sediments are poorly constrained to about 118−100 ka, i.e., at the marine isotope stage (MIS) 5e/5d boundary. Moreover, sediments at Lac du Bouchet maar, France and along the Portuguese margin reveal what may be a "post-Blake" excursion at about 105−95 ka. The excursional directions are associated with a prominent paleointensity minimum between about 125 and 95 ka in global stacked records. Lava flow recordings of the Blake excursion(s) have, however, been questionable because precise ages required for correlation with these sediment records are lacking. To establish new, independent records of the Blake excursion, and link these into a larger Quaternary GITS, we have undertaken 40Ar/39Ar incremental heating and unspiked K-Ar experiments on groundmass from the transitionally magnetized Inzolfato flow on Lipari Island. We also obtained 40Ar/39Ar incremental heating results for a lava flow on Amsterdam Island originally thought to record the Mono Lake excursion and from the transitionally magnetized El Calderon basalt flow, New Mexico that was K-Ar dated by Champion et al. (1988) at 128 ± 66 ka. Unspiked K-Ar ages of four samples from the Inzolfato flow are 102.5 ± 4.7, 101.3 ± 3.3, 97.1 ± 2.6, and 96.8 ± 3.1 ka and thus indistinguishable from one another. 40Ar/39Ar results are more complex, with three samples yielding discordant age spectra. Based on incremental heating data obtained in both the UW-Madison and Gif-sur-Yvette 40Ar/39Ar laboratories, a fourth sample yields six concordant age plateaus and a weighted mean age of 105.2 ± 1.4 ka that we take as the best estimate of time since the flow erupted. Five 40Ar/39Ar incremental heating experiments on the Amsterdam Island lava yield a plateau age of 120 ± 12 ka, whereas ages from two sites in the Calderon flow are 112 ± 23 and 101 ± 14 ka, together giving a weighted mean of 104 ± 12 ka. The age of 120 ± 12 ka from Amsterdam Island, though imprecise, correlates with the Blake excursion. In contrast, the 104-105 ka age obtained from both Lipari and New Mexico indicates that these lavas record a younger period of dynamo instability, most probably associated with the post-Blake excursion. These radioisotopic ages are consistent with the astronomical ages of two paleointensity minima in the PISO-1500 global stack. Our findings indicate that the Blake and post-Blake excursions are both global features of past geodynamo behavior and support the hypothesis that Brunhes chron excursions are temporally clustered into two groups of at least a half-dozen each spanning over 220 to 30 ka and 720 to 520 ka.
ISSN: 1871-1014

hal-01054336
https://hal.archives-ouvertes.fr/hal-01054336
DOI : 10.1016/j.quageo.2012.12.005

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Liver X Receptors (LXRs) α and β and the Peroxisome Proliferator-Activated Receptor α (PPARα) are transcription factors that belong to class II nuclear receptors. They drive the expression of genes involved in hepatic lipid homeostasis and therefore are important targets for the prevention and treatment of nonalcoholic fatty liver disease (NAFLD). LXRs and PPARα are regulated by endogenous ligands, oxysterols and fatty acid derived molecules, respectively. In the liver, pharmacological activation of LXRs leads to the over-expression of genes involved in de novo lipogenesis, while PPARα is critical for fatty acid catabolism in nutrient deprivation. Even if these two nuclear receptors seemed to play opposite parts, recent studies have highlighted that PPARα also influence the expression of genes involved in fatty acids synthesis. In this study, we used pharmacological approaches and genetically engineered mice to investigate the cross-talk between LXRs and PPARα in the regulation of genes responsible for lipogenesis. We first investigated the effect of T0901317 and fenofibrate, two synthetic agonists of LXRs and PPARα, respectively. As expected, T0901317 and fenofibrate induce expression of genes involved LXR-dependent and PPARα-dependent lipogenic responses. Considering such overlapping effect, we then tested whether LXR agonist may influence PPARα driven response and vice versa. We show that the lack of PPARα does not influence the effects of T0901317 on lipogenic genes expression. However, PPARα deficiency prevents the up-regulation of genes involved in ω-hydroxylation that are induced by the LXR agonist. In addition, over-expression of lipogenic genes in response to fenofibrate is decreased in LXR knockout mice as well as the expression of PPARα target genes involved in fatty acid oxidation. Altogether, our work provides in vivo evidence for a central interconnection between nuclear receptors that drive hepatic lipid metabolism in response to oxysterol and fatty acids.
ISSN: 0300-9084

inserm-00872582
http://www.hal.inserm.fr/inserm-00872582
DOI : 10.1016/j.biochi.2012.09.028
PUBMED : 23063693

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The influence of redox alteration on the growth and proteomic pattern of Listeria monocytogenes was investigated. A redox shock was induced in cultures by addition of 3mM ferricyanide (FeCN) and 6mM dithiothreitol (DTT) to increase or to decrease respectively the redox potential naturally occurring at the beginning of growth. In both conditions, the reducing and oxidizing redox shock had a strong influence, decreasing the maximum growth rate by half compared to a control culture. The proteomic analysis of L. monocytogenes performed by two-dimensional difference gel electrophoresis (2D-DIGE) exhibited twenty-three proteins differentially expressed (P<0.05), among these, many were oxidoreductases, and proteins involved in cellular metabolism (glycolysis, protein synthesis), detoxification (kat) or adhesion (Lmo1634).
ISSN: 1874-3919

hal-00877138
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877138
DOI : 10.1016/j.jprot.2012.11.010
PUBMED : 23195917

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The morphogenetic evolution of the Lesser Caucasus has been strongly influenced by Plio-Quaternary volcanic and tectonic events and Pleistocene glaciations. Fluvio-lacustrine environments, indicated by diatomaceous deposits, prevailed in the Syunik region of southern Armenia during the Pliocene and Pleistocene. The Pleistocene diatomaceous deposits studied contain leaf impressions and pollen, allowing local palaeoclimatic reconstructions. The chronology of morphogenetic events has been determined by 17 radiometric dates (K/Ar, Ar/Ar, U/Th), palaeomagnetic investigations and is placed in a spatial context by a detailed geomorphological map and a 24-km geological transect of the Vorotan valley, the main area studied. Before 1.21 Ma, tectonic movements (antecedents of the lower part of the Vorotan valley) generated extensive lake formations with diatomaceous deposits. From 993 ka, volcanic eruptions produced lava flows that covered the fluvio-lacustrine accumulations. During Marine Isotopic Stages 12, 6 and 4, glaciers and fluvio-glacial deposits were probably present overall the principal uplands and valleys of southern Armenia. At 53.68 ka (MIS 3), 12.6 ka, 10.78 ka and 4.14 ka (MIS 1), the development of travertines on some slopes and in some valleys highlights temperate and humid climatic phases. Palaeobotanical studies of leaf and pollen floras show that the vegetation changed several times from forested to steppic phases in response to the climate oscillations of the Lower Pleistocene. This work proposes a first morphogenic and palaeoclimatic reconstruction from the lower Pleistocene to the Postglacial period, when the first settlements of the population in the Lesser Caucasus were influenced by tectono-volcanic events, lake level changes and glacialeinterglacial oscillations forced by the obliquity orbital parameter (41 ky cycles).
ISSN: 1040-6182

hal-00481939
https://hal.archives-ouvertes.fr/hal-00481939
DOI : 10.1016/j.quaint.2010.02.008