Agency: Cordis | Branch: FP7 | Program: MC-CIG | Phase: FP7-PEOPLE-2011-CIG | Award Amount: 100.00K | Year: 2011
Type 2 diabetes (T2D) is a growing global epidemic and new prevention and therapeutic strategies are urgently needed. Insulin resistance is present in high-risk individuals years before the onset of T2D, making the characterization of the complex pathophysiology of insulin resistance a key element of future prevention efforts. The overall goal of our project is to identify and characterize novel molecular mechanisms underlying the development of insulin resistance to find specific targets for prevention and therapeutic strategies. Our analysis of the plasma metabolome of humans at risk for T2D suggests that reductions in betaine levels can contribute to insulin resistance. Consistent with this hypothesis, preliminary studies show that betaine supplementation improves insulin sensitivity and whole-body energy expenditure in a mouse model of diet-induced obesity. First, we propose to determine the mechanisms mediating the beneficial effects of betaine on insulin sensitivity in a diet-induced obese mouse model. For this purpose, C57BL/6 mice will be fed either chow or high-fat diet with or without betaine supplementation. Whole-body and tissue-specific betaine effects will be analyzed to characterize the mechanisms of betaine action. Second, we will apply next generation sequencing of mRNA to analyze the muscle transcriptome associated with high fat feeding and betaine supplementation. As metabolic and molecular changes induced by betaine will be intimately linked to insulin sensitivity, this technique will identify novel genes, alternative splicing isoforms and pathways potentially involved in the development of muscle insulin resistance. This project will constitute a critical first step for future studies aimed at determining whether betaine supplementation is effective in preventing insulin resistance and progression to T2D in humans. Furthermore, it will identify novel targets for designing prevention and therapeutic strategies for the development of T2D.
Pomarol-Clotet E.,Research Unit |
Canales-Rodriguez E.J.,Research Unit |
Salvador R.,Research Unit |
Sarro S.,Research Unit |
And 8 more authors.
Neuroimaging studies have found evidence of altered brain structure and function in schizophrenia, but have had complex findings regarding the localization of abnormality. We applied multimodal imaging (voxel-based morphometry (VBM), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) combined with tractography) to 32 chronic schizophrenic patients and matched healthy controls. At a conservative threshold of P0.01 corrected, structural and functional imaging revealed overlapping regions of abnormality in the medial frontal cortex. DTI found that white matter abnormality predominated in the anterior corpus callosum, and analysis of the anatomical connectivity of representative seed regions again implicated fibres projecting to the medial frontal cortex. There was also evidence of convergent abnormality in the dorsolateral prefrontal cortex, although here the laterality was less consistent across techniques. The medial frontal region identified by these three imaging techniques corresponds to the anterior midline node of the default mode network, a brain system which is believed to support internally directed thought, a state of watchfulness, and/or the maintenance of one's sense of self, and which is of considerable current interest in neuropsychiatric disorders. © 2010 Macmillan Publishers Limited All rights reserved. Source
Navarra J.,Fundacio Sant Joan de Deu |
Navarra J.,University of Oxford |
Alsius A.,University of Barcelona |
Soto-Faraco S.,Catalan Institution for Research and Advanced Studies |
And 2 more authors.
Currently, one of the most controversial topics in the study of multisensory integration in humans (and in its implementation in the development of new technologies for human communication systems) concerns the question of whether or not attention is needed during (or can modulate) the integration of sensory signals that are presented in different sensory modalities. Here, we review the evidence on this question, focusing specifically on the integration of auditory and visual information during the perception of speech. Contrary to the mainstream view that has been prevalent for the last 30 years or so, recent studies have now started to reveal that attentional resources are, in fact, recruited during audiovisual multisensory integration, at least under certain conditions. Finally, considering all of the available evidence, we discuss the extent to which audiovisual speech perception should be considered to represent a 'special' case of audiovisual, and more generally, of multisensory integration. © 2009 Elsevier B.V. All rights reserved. Source
Salvador R.,Benito Menni C.A.S.M. CIBERSAM |
Sarro S.,Benito Menni C.A.S.M. CIBERSAM |
Gomar J.J.,Benito Menni C.A.S.M. CIBERSAM |
Ortiz-Gil J.,Benito Menni C.A.S.M. CIBERSAM |
And 6 more authors.
Human Brain Mapping
Abnormal interactions between areas of the brain have been pointed as possible causes for schizophrenia. However, the nature of these disturbances and the anatomical location of the regions involved are still unclear. Here, we describe a method to estimate maps of net levels of connectivity in the resting brain, and we apply it to look for differential patterns of connectivity in schizophrenia. This method uses partial coherences as a basic measure of covariability, and it minimises the effect of major physiological noise. When overall (net) connectivity maps of a sample of 40 patients with schizophrenia were compared with the maps from a matched sample of 40 controls, a single area of abnormality was found. It is an area of patient hyper-connectivity and is located frontally, in medial and orbital structures, clearly overlapping the anterior node of the default mode network (DMN). When this area is used as a region of interest in a second-level analysis, it shows functional hyper-connections with several cortical and subcortical structures. Interestingly, the most significant abnormality is found with the caudate, which has a bilateral pattern of abnormality, pointing to a possible DMN-striatum deviant relation in schizophrenia. However, hyper-connectivity observed with other regions (right hippocampus and amygdala, and other cortical structures) suggests a more pervasive alteration of brain connectivity in this disease. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. Source
Sans-Sansa B.,FIDMAG Germanes Hospitalaries |
McKenna P.J.,FIDMAG Germanes Hospitalaries |
Canales-Rodriguez E.J.,FIDMAG Germanes Hospitalaries |
Ortiz-Gil J.,FIDMAG Germanes Hospitalaries |
And 6 more authors.
Background: Formal thought disorder (FTD) in schizophrenia has been found to be associated with volume reductions in the left superior temporal cortex. However, there have been negative findings and some studies have also found associations in other cortical regions. Method: Fifty-one schizophrenic patients were evaluated for presence of FTD with the Thought, Language and Communication (TLC) scale and underwent whole-brain structural MRI using optimized voxel-based morphometry (VBM). Fifty-nine matched healthy controls were also scanned. Results: Compared to 31 patients without FTD (global TLC rating 0 or 1), 20 patients with FTD (global TLC rating 2-5) showed clusters of volume reduction in the medial frontal and orbitofrontal cortex bilaterally, and in two left-sided areas approximating to Broca's and Wernicke's areas. The pattern of FTD-associated volume reductions was largely different from that found in a comparison between the healthy controls and the patients without FTD. Analysis of correlations within regions-of-interest based on the above clusters indicated that the 'fluent disorganization' component of FTD was correlated with volume reductions in both Broca's and Wernicke's areas, whereas poverty of content of speech was correlated with reductions in the medial frontal/orbitofrontal cortex. Conclusions: The findings point to a relationship between FTD in schizophrenia and structural brain pathology in brain areas involved in language and executive function. © 2013 Elsevier B.V. Source