Regulation of gene expression by glucose

International audienceIn addition to its metabolic function, glucose modulates gene expression which is crucial in adapting cells to variations in glycaemia. We summarize recent advances in our understanding of regulation of gene expression by glucose

The ubiquitin-proteasome pathway is a new partner for the control of insulin signaling.

International audienceInsulin signaling is a transitory effect that has to be tightly controlled in magnitude and duration in order to maintain cell homeostasis. Recent reports have demonstrated that members of the ubiquitin-proteasome pathway represent new partners that have to be taken into account for the regulation of insulin action

Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias

Aims The timecourse of left atrial Pitx2 down-regulation in the setting of atrial tachyarrhythmias remains unknown. Accordingly, we aimed to assess the age dependency of left atrial Pitx2 expression in an experimental model of spontaneous atrial tachyarrhythmias in rats.Methods and results Atrial sampling was performed in three groups (n = 4 each) of young (14-week-old), adult (24-week-old), and ageing (48-week-old) spontaneously hypertensive rats (SHRs), in which we previously demonstrated the age dependency of spontaneous atrial tachyarrhythmias, and three groups (n = 4 each) of age-matched normotensive Wistar-Kyoto (WKY) rats. mRNA expression of Pitx2 was studied using real-time polymerase chain reaction. Ageing SHRs presented significantly lower left atrial Pitx2 expressions compared with age-matched WKY rats (P = 0.02), while no significant difference was observed between young or adult SHRs and age-matched WKY rats (both P > 0.05). Among SHRs, Pitx2 expressions showed a progressive, age-dependent decrease (34.9 +/- 6.7 in young SHRs, 17.1 +/- 3.6 in adult SHRs, and 10.7 +/- 1.7 in ageing SHRs, P = 0.04) and were significantly negatively correlated with both age (Spearman r = -0.86, P < 0.01) and heart weight (Spearman r = -0.76, P < 0.01).Conclusion The present study suggests the presence of age-dependent left atrial Pitx2 down-regulation in SHRs. The strong negative correlation between left atrial Pitx2 expression and heart weight among SHRs may indicate a link between long-standing arterial hypertension and Pitx2-related atrial arrhythmogenicity

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

Intruducere Deși înaintarea în vârstă este asociată cu creșterea prevalenței aritmiilor cardiace, evenimentele transcriptomice care stau la baza acestui proces rămân neelucidate. Pentru a identifica aceste mecanisme am realizat analiza expresiei ARNm la nivelul miocardului atrial și ventricular la șobolani Wistar-Kyoto (WKY) de diferite vârste. Metodă: Expresiile ARNm a 89 de gene au fost analizate prin TLDA utilizând eșantioane atriale și ventriculare de la 3 grupuri (n=4 fiecare) de șobolani WKY tineri, adulți și vârstnici. Rezultate: Din cele 89 de gene, 40 și respectiv 64 de gene au prezentat expresii stabile la nivel atrial și respectiv ventricular. Toate genele exprimate diferit în atriile șobolanilor WKY au prezentat o up-regulare cu înaintarea în vârstă, în special genele care codifică canale de K+, Ca2+, Na+ și colagenul de tip 6. Expresia atrială a 19 gene a fost corelată pozitiv cu vârsta. Analiza transcriptomică ventriculară a evidențiat un echilibru între genele up-regulate și down-regulate codificând aceleași canale ionice. Concluzii: Rezultatele noastre indică un răspuns transcripțional atrial, dar nu și ventricular, caracterizat prin up-regulare odată cu înaintarea în vârstă. Aceste rezultate sugerează că cele două cavități sunt supuse unor programe de remodelare moleculară diferite. Atriile îmbătrânite au prezentat un profil transcriptomic sugestiv pentru o predispoziție crescută pentru aritmii, precum up-regularea genelor care codifică If, ICa-L, ICa-P, INa și colagenul, în timp ce transcriptomul ventricular nu pare să fie sever alterat de înaintarea în vârstă. Aceste observații ar putea explica predispoziția mai mare pentru aritmii atriale decât ventriculare la vârstnici

Analysis of the microRNA signature in left atrium from patients with valvular heart disease reveals their implications in atrial fibrillation

International audienceBackground Among the potential factors which may contribute to the development and perpetuation of atrial fibrillation, dysregulation of miRNAs has been suggested. Thus in this study, we have quantified the basal expressions of 662 mature human miRNAs in left atrium (LA) from patients undergoing cardiac surgery for valve repair, suffering or not from atrial fibrillation (AF) by using TaqMan (R) Low Density arrays (v2.0). Results Among the 299 miRNAs expressed in all patients, 42 miRNAs had altered basal expressions in patients with AF. Binding-site predictions with Targetscan (conserved sites among species) indicated that the up- and down-regulated miRNAs controlled respectively 3,310 and 5,868 genes. To identify the most relevant cellular functions under the control of the altered miRNAs, we focused on the 100 most targeted genes of each list and identified 5 functional protein-protein networks among these genes. Up-regulated networks were involved in synchronisation of circadian rythmicity and in the control of the AKT/PKC signaling pathway (i.e., proliferation/adhesion). Down-regulated networks were the IGF-1 pathway and TGF-beta signaling pathway and a network involved in RNA-mediated gene silencing, suggesting for the first time that alteration of miRNAs in AF would also perturbate the whole miRNA machinery. Then we crossed the list of miRNA predicted genes, and the list of mRNAs altered in similar patients suffering from AF and we found that respectively 44.5% and 55% of the up- and down-regulated mRNA are predicted to be conserved targets of the altered miRNAs (at least one binding site in 3'-UTR). As they were involved in the same biological processes mentioned above, these data demonstrated that a great part of the transcriptional defects previously published in LA from AF patients are likely due to defects at the post-transcriptional level and involved the miRNAs. Conclusions Our stringent analysis permitted us to identify highly targeted protein-protein networks under the control of miRNAs in LA and, among them, to highlight those specifically affected in AF patients with altered miRNA signature. Further studies are now required to determine whether alterations of miRNA levels in AF pathology are causal or represent an adaptation to prevent cardiac electrical and structural remodeling

Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle

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Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle

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Impacts métaboliques à court terme de deux émulsifiants alimentaires riches en acide α-linolénique chez la souris

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Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoiins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as alpha-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods

Impact of the addition of vegetable lecithin in oil on lipid metabolism and the bioavailability of an essential fatty acid: alpha-linolenic acid

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