63 research outputs found
Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue
Vitamin A & vitamin D : overall impact on adipocyte inflammation associated with obesity
Des Ă©tudes Ă©pidĂ©miologiques ont montrĂ© que lâobĂ©sitĂ© est associĂ©e Ă une diminution du taux plasmatique en rĂ©tinol et en 25 hydroxyvitamine D. Il a Ă©tĂ© Ă©galement montrĂ© quâil existe une corrĂ©lation entre carences en vitamines A et D et de nombreuses pathologies notamment lâinsulino-rĂ©sistance et lâinflammation. Notre hypothĂšse Ă©tait de savoir sâil existe un lien entre vitamines A/D et inflammation au niveau du tissu adipeux (TA). Quelques Ă©tudes avaient montrĂ© que les formes actives de ces vitamines limitaient lâinflammation au niveau du TA en sâintĂ©ressant uniquement Ă quelques marqueurs inflammatoires. Nous avons alors voulu Ă©tudier lâimpact global de ces deux vitamines sur le transcriptome dâadipocytes soumis Ă un stress inflammatoire en ayant recours Ă des approches haut dĂ©bit. Nous avons montrĂ© que les vitamines A et D limitent lâinflammation au niveau des adipocytes humains et murins, in vitro, en diminuant lâexpression de cytokines et de chimiokines ce qui induit une diminution de la migration macrophagique. Nous avons confirmĂ© lâeffet anti-inflammatoire de ces deux vitamines in vivo en ayant recours Ă des modĂšles murins dâinflammation chronique et aigĂŒe. Nous nous sommes ensuite intĂ©ressĂ©s aux microARN dĂ©rĂ©gulĂ©s dans les adipocytes en condition inflammatoire. Nous avons mis en Ă©vidence le rĂŽle clĂ© du miR-155 dans lâamplification du signal inflammatoire. Nous avons montrĂ© que les vitamines A et D rĂ©duisent lâexpression du miR-155 mais Ă©galement celle des miR-146a et miR-150 au niveau des adipocytes murins et humains. Enfin, nous avons montrĂ© que les effets anti-inflammatoires des vitamines A et D sont mĂ©diĂ©s par une inhibition de la voie de signalisation NF-ÎșB.Epidemiological studies have shown that obesity is associated with a decrease in plasma retinol and 25-hydroxyvitamin D. It was also shown a correlation between insufficiencies of vitamins A and D and many diseases including insulin resistance and inflammation. Our working hypothesis was to test whether there is a link between vitamins A/D and inflammation in adipose tissue. Some studies have shown that the active forms of vitamins A and D limited inflammation in adipose tissue by looking only at few inflammatory markers. On the basis of these promising preliminary results, we wanted to examine the overall impact of these two vitamins on the transcriptome of adipocytes submitted to an inflammatory stress by using high-throughput methodologies. We have shown that vitamins A and D are able to limit inflammation in human and murine adipocytes, in vitro, by decreasing the expression of cytokines and chemokines which induces a decrease of macrophage migration. We have confirmed the anti-inflammatory effect of these two vitamins in vivo by using of chronic and acute inflammation mouse models. We then focused on microRNA which were deregulated in adipocytes in inflammatory conditions. We highlighted the key role of miR-155 in the amplification of the inflammatory signal. We have shown that vitamins A and D reduce the expression of miR-155 but also that of miR-146a and miR-150 in murine and human adipocytes. Finally, we showed that the anti-inflammatory effects of vitamins A and D are mediated by an inhibition of the signaling pathway NF-ÎșB
MicroRNAs in Endocrine Disorders
The endocrine system is a network of glands that produces and releases hormones, which helps to control many important body functions. The diseases associated with the endocrine system may result from a dysfunction at different levels during release or action of the hormones. The burdens of endocrine disease such as obesity or type 2 diabetes are believed to arise through a complex interplay between genetics and epigenetic predisposition, environment, nutrition, as well as lifestyle. Therefore, understanding the molecular mechanisms for the onset of endocrine disease will provide new insights for prevention and treatment of these endocrine disorders. There is a growing concern about the dysregulation of micro-RNAs (miRNAs) in endocrine diseases. miRNAs are short noncoding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3âČ-untranslated regions of the target mRNAs. This chapter aims to provide recent data about the potential involvement of miRNAs in endocrine diseases, such as metabolic syndrome (obesity and type 2 diabetes) or neuroendocrine disorders
Vitamin D modulates adipose tissue biology: possible consequences for obesity?
International audienceCross-sectional studies depict an inverse relationship between vitamin D (VD) status reflected by plasma 25-hydroxy-vitamin D and obesity. Furthermore, recent studies in vitro and in animal models tend to demonstrate an impact of VD and VD receptor on adipose tissue and adipocyte biology, pointing to at least a part-causal role of VD insufficiency in obesity and associated physiopathological disorders such as adipose tissue inflammation and subsequent insulin resistance. However, clinical and genetic studies are far less convincing, with highly contrasted results ruling out solid conclusions for the moment. Nevertheless, prospective studies provide interesting data supporting the hypothesis of a preventive role of VD in onset of obesity. The aim of this review is to summarise the available data on relationships between VD, adipose tissue/adipocyte physiology, and obesity in order to reveal the next key points that need to be addressed before we can gain deeper insight into the controversial VD-obesity relationship
Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity?
International audienc
Murine double minute-2 mediates exercise-induced angiogenesis in adipose tissue of diet-induced obese mice
International audienceThis study aimed to determine the effects of physical exercise on the angio-adaptive response in adipose tissue following weight loss in a mouse model of diet-induced obesity. We hypothesized that physical exercise stimulates angiogenesis through the regulation of Vascular endothelial growth factor-A (VEGF-A) pro-/Thrombospondin-1 (TSP-1) anti-angiogenic signal under the control of the Murine double-minute 2/Forkhead box Os (Mdm2/FoxOs) axis, as reported in skeletal muscle
Proposal of a bioinformatics approach to predict molecular mechanisms involved in inflammatory response: case of ATRA and 1,25(OH)2D in adipocytes
Several inflammatory markers such as cytokines, chemokines, and microRNAs (miRNAs) are well known to be induced during obesity and are strongly linked to their comorbidities. Among many others factors, the micronutrient status is suspected to reduce obesity-associated inflammation via blunting inflammatory signalling pathways. This is notably the case for active forms of vitamin A (all-trans retinoic acid ATRA) and vitamin D (1,25(OH)2D) as previously shown. In the present study, we aimed to implement a new bioinformatics approach to unveil commonly regulated signalling pathways through a combination of gene and miRNA expression sets impacted by ATRA and 1,25(OH)2D in adipocytes. In a first set of experiments, we focused only our attention on ATRA and demonstrated that it reduced LPS-mediated miRNA expression (miR-146a, miR-150, and miR-155) in mouse adipose tissue, in adipocyte cultures, and in adipocyte-derived vesicles. This result was confirmed in TNFα-induced miRNA in human adipocytes. Then, bioinformatic analysis highlighted that both ATRA and 1,25(OH)2D-regulated genes and miRNA converge to the canonical ânuclear factor Kappa B (NF-ÎșB) signalling pathway.â Altogether, these results showed that ATRA has anti-inflammatory effects on miRNA expression. In addition, the proposed bioinformatic model converges to NF-ÎșB signalling pathway that has been previously demonstrated to be regulated by ATRA and 1,25(OH)2D, thus confirming the interest of such approach
Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity?
International audienc
Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity?
International audienceObjective This study aimed to explore the role of nine microRNAs (miRNAs) in microparticles (MPs) on the efficacy of aerobic exercise in the regulation of inflammation and vascular function in obesity. Methods Sedentary women with normal weight (nâ=â6, BMIââ30 kg/m2) were recruited at F. Hached Hospital (Sousse, Tunisia) and enrolled in an 8âweek aerobic program. Vascular function was assessed using laser Doppler flowmetry/iontophoresis, circulating MPs by flow cytometry, miRNAs by realâtime polymerase chain reaction, and inflammation by ELISA, before and after exercise. Results Women with obesity presented with high prevalence of cardiovascular risk factors and a higher circulating MP level compared with healthy subjects. The MP miRNA profile was significantly different in the two groups. Exercise reduced BMI and inflammation in both groups and significantly improved endothelialâdependent response (acetylcholine cutaneous vascular conductance) for healthy subjects, with a trend for women with obesity. Circulating MP level was increased after exercise, and miRNA expression was differentially modulated in both populations. Pearson analysis revealed a correlation between MPs miRâ124a and miR150 and adiponectin, TNFα, or ILâ6 levels. Conclusions The relation between MPs and miRNA profile, inflammation, vascular function, and exercise is of particular interest for defining âmiRNA biomarker signatureâ in patients with cardiovascular disease who are potentially susceptible to respond to exercise
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