Collantes, M. (María)

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    Decreased glucose-derivate uptake in primary somatosensorial cortex in the brain of female AIP mice. | International Porphyrins and Porphyria Meeting (10-13 April 2011. Cardiff, Wales, UK)
    (2011-04-13) Pozo, M.A. (Miguel Ángel); Delgado, M. (Mercedes); Benito, M. (Marina); Collantes, M. (María); Lanciego, J.L. (José Luis); Peñuelas-Sanchez, I. (Ivan); Desco, M. (Manuel); Prieto-Azcárate, E. (Elena); Molinet-Dronda, F. (Francisco); Unzu, C. (Carmen); Prieto, J. (Jesús); Enriquez-de-Salamanca, R. (Rafael); Fontanellas-Romá, A. (Antonio); Garcia-Garcia, L. (Luis); Rodriguez, I. (Ignacio)
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    Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function
    (Public Library Science, 2010-05-16) Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Becerril, S. (Sara); Frühbeck, G. (Gema); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Sainz, N. (Neira)
    Abstract Background: Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS) gene in the regulation of energy balance in ob/ob mice. Methods and Findings: Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p,0.05), decreased amounts of total fat pads (p,0.05), lower food efficiency rates (p,0.05) and higher rectal temperature (p,0.05) than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16), a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferatoractivated receptor c coactivator-1 a (Pgc-1a), sirtuin-1 (Sirt-1) and sirtuin-3 (Sirt-3). Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3) were upregulated in brown adipose tissue (BAT) of DBKO mice as compared to ob/ob rodents. Conclusion: Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement.
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    Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice
    (Wiley, 2021) Collantes, M. (María); Moreno-Aliaga, M. J. (María Jesús); Gil-Iturbe, E. (Eva); Dalli, J. (Jesmond); Félix-Soriano, E. (Elisa); Fernandez-Galilea, M. (Marta); Castilla-Madrigal, R. M. (Rosa María); Sainz, N. (Neira); Ly, L. (Lucy)
    Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to chronic unresolved inflammation, which could be mediated by an impaired production of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs, Resolvins-Rvs, Protectins-PDs, and Maresins-MaRs. Our aim was to characterize the changes in BAT SPMs signatures and their association with BAT dysfunction during aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic acid (DHA)-rich diet. Lipidomic, functional, and molecular studies were performed in BAT of 2-and 18-month- old lean (CT) female mice and in 18-month- old diet-induced obese (DIO) mice fed with a high-fat diet (HFD), or a DHA-enriched HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice, while DHA partially restored them. Arachidonic acid (AA)-derived LXs and DHA-derived MaRs and PDs were the most abundant SPMs in BAT of young CT mice.Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice compared to young CT mice. Some of the SPMs most significantly reduced in obese-aged mice included LXB4, MaR2, 4S,14S-diHDHA, 10S,17S-diHDHA (a.k.a. PDX), and RvD6. In contrast, DHA increased DHA-derived SPMs, without modifying LXs. However, MicroPET studies showed that DHA was not able to counteract the impaired cold exposure response in BAT of obese-aged mice. Our data suggest that a defective SPMs production could underlie the decrease of BAT activity observed in obese-aged mice, and highlight the relevance to further characterize the physiological role and therapeutic potential of specific SPMs on BAT development and function.
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    Monoaminergic and metabolic Positron Emission Tomography of unilateral and bilateral 6-OHDA rat models of Parkinson's disease: a longitudinal in-vivo study. | 15º Congreso Nacional de la Sociedad Española de NeuroCiencia (25-27 de Septiembre de 2013. Oviedo, Spain)
    (2013-09-26) Delgado, M. (Mercedes); Quiroga-Varela, A. (Ana); Juri, C. (Carlos); Obeso, J.A. (José A.); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Prieto-Azcárate, E. (Elena); Molinet-Dronda, F. (Francisco); Gago, B. (Belén); Iglesias, E. (Elena)
    Parkinson´s disease (PD) is characterized by nigro-striatal loss and dopaminergic striatal depletion. The aim of this work is to characterize in-vivo a time-course pattern of functional changes associated with dopaminergic striatal reduction in rat models of PD using Positron Emission Tomography (PET). Forty-four male Sprague-Dawley rats (300-350gr) were used. PET imaging with monoaminergic (11C-(+)-α-dihydrotetrabenazine; 11C-DTBZ) and metabolic (18F-fluorodeoxyglucose; 18F-FDG) radiotracers were performed in a longitudinal study during 6 weeks of the following groups: a) unilaterally lesioned rats by injection of 4µg/4µl (low dose) and 8µg/4µl (high dose) of 6-hydroxydopamine (6-OHDA) in the left median forebrain bundle; and b) bilateral lesion model, in rats receiving intraventricular injection of 100µg/4µl/day of 6-OHDA during 7 days. At the 8th week, the glucose metabolism was also evaluated ex vivo by 18F-FDG autoradiography. Bilaterally lesioned animals were not assessed with metabolic analyses. 11C-DTBZ PET images showed a significant decrease of Striatal Binding (SB) values one week after the lesion (35% SB in the low and 20% SB in the high dose group of unilateral model, and 50% SB in the bilateral model). In the 6th week, no significant differences in these values were found in the unilaterally lesion rats, whereas animals with bilateral lesion showed a higher binding value (65% SB). Remarkably, the metabolic PET study in the unilateral model revealed hypometabolism in ipsilateral somatosensory cortex and hypermetabolism in contralateral entorhinal cortex since the 2nd week onwards. Additionally, the autoradiography analysis showed hypometabolism in bilateral somatosensory cortex and ipsilateral caudate-putamen, motor cortex and thalamus, and also hypermetabolism in the contralateral entorhinal cortex. 11C-DTBZ PET is a sensitive method to ascertain dopaminergic depletion in both the bilateral and, unilateral 6-OHDA rat models. 18F-FDG studies showed a dynamic metabolic pattern that can provide useful in vivo information to monitor brain changes.
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    Síntesis simplificada de 11C-(+)-α-dihidrotetrabenazina para su utilización como radioligando PET de los transportadores vesiculares de monoaminas
    (Elsevier, 2008) Areses, P. (P.); Marti-Climent, J.M. (Josep María); Obeso, J.A. (José A.); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Quincoces, G. (Gemma); Richter, J.A. (José Ángel); Ecay, M. (Margarita); Blesa, J. (Javier); Martino, E. (E.); Álvarez, L. (Lluis)
    La dihidrotetrabenazina (2-hidroxi-3-isobutil-9,10-dimetoxi-1,3,4,6,7-hexahidro-11bH-benzo[a]-quinolizina, DTBZ) se ha convertido en el ligando ideal de los transportadores presinápticos de monoaminas (VMAT2) debido a su elevada afinidad de unión y su lipofilicidad. Objetivo. Desarrollar un procedimiento de síntesis automático para el marcaje con carbono-11 de la DTBZ para utilizarla como marcador en el estudio in vivo mediante tomografía por emisión de positrones de pérdidas neuronales en modelos animales de enfermedad de Parkinson. Material y métodos. Se ha diseñado un nuevo método de síntesis totalmente automatizado para la obtención de 11C-(+)DTBZ. La reacción de metilación del precursor ­(+)desmetildihidrotetrabenazina­ se lleva a cabo a temperatura ambiente, a partir de la obtención de 11CH3I que utilizamos como precursor primario, en presencia de dimetilsulfóxido e hidróxido de potasio. Para los procesos de purificación se han utilizado cartuchos de extracción en fase sólida alúmina y los disolventes residuales del producto final se eliminaron mediante evaporación bajo flujo de helio. Resultados. De las 54 síntesis realizadas se han obtenido, con un tiempo de bombardeo de 5 minutos, y 6 minutos de síntesis tras la obtención de 11CH3I, unas producciones medias de 1,94 ± 0,13 GBq de 11C-(+)DTBZ, estéril, apirógeno y con una pureza radioquímica > 99 %. Conclusiones. Este nuevo procedimiento de síntesis es rápido y simple, ya que para la purificación final se han optimizado técnicas que permitieran la eliminación de los disolventes residuales basándonos en su polaridad y es aplicable a otras síntesis automáticas para la obtención de otros compuestos marcados mediante reacciones de metilación.
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    Simple automated system for simultaneous production of 11C-labeled tracers by solid supported methylation
    (Elsevier, 2006-02-15) Marti-Climent, J.M. (Josep María); Serra, P. (Patricia); Valero, M. (Marta); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Quincoces, G. (Gemma); Richter, J.A. (José Ángel); Garcia-Velloso, M. J. (María José); Arbizu, J. (Javier)
    We herein describe a simple setup for the automated simultaneous synthesis of l-[methyl-11C]methionine and N-[methyl-11C]choline by solid-supported methylation . The setup is extremely simple and easy to adapt to other automated systems and due to its versatility, the method can be utilized for the production of other radiopharmaceuticals requiring a simple [11C]methylation step. Furthermore, it can be used for multiple simultaneous synthesis.
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    Construction of different radionuclide templates of rat brains and their use on a new statistic parametric mapping analysis protocol for PET studies. | International WorkshopCNA´10: Bio-medical applications of Micro-PET (20-21 September 2010. Sevilla, Spain)
    (2010-09-20) Pozo, M.A. (Miguel Ángel); Delgado, M. (Mercedes); Juri, C. (Carlos); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Prieto-Azcárate, E. (Elena); Molinet-Dronda, F. (Francisco); Fernandez, M.E. (M. E.); Garcia-Garcia, L. (Luis)
    This work shows the development of protocols to create new 18F‐FDG and 11C‐DTBZ (dyhidrotetrabenazine, a VMAT2 transporter ligand) templates of rat brain for spatial normalisation and definition of standardised areas in images used for setting up SPM analysis of PET data.
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    Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice
    (Elsevier, 2023) Martinez, J.A. (José Alfredo); Villarroya, F. (Francesc); Escoté-Miró, X. (Xavier); Quesada-López, T. (Tania); Laiglesia-González, L.M. (Laura María); Lorente-Cebrian, S. (Silvia); Collantes, M. (María); Moreno-Aliaga, M. J. (María Jesús); Dalli, J. (Jesmond); Arbones-Mainar, J.M. (José M.); Félix-Soriano, E. (Elisa); Rodriguez-Ortigosa, C.M. (Carlos M.); Santamaría, E. (Eva); Martínez-Fernández, L. (Leyre); Fernandez-Galilea, M. (Marta); Vázquez, S. (Sergio); Herrero, L. (Laura); Valverde, A.M. (Ángela M.); Sainz, N. (Neira); Colón-Mesa, I. (Ignacio)
    Objective: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. Methods: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6 / ) mice. Results: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6 / mice. Conclusions: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.
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    Nutritional Interventions with Bacillus coagulans Improved Glucose Metabolism and Hyperinsulinemia in Mice with Acute Intermittent Porphyria
    (2023) Riezu-Boj, J.I. (José Ignacio); Di-Pierro, E. (Elena); Collantes, M. (María); Moreno-Aliaga, M. J. (María Jesús); Peñuelas-Sanchez, I. (Ivan); Solares, I. (Isabel); Avila, M.A. (Matías Antonio); Córdoba-Quiñones, K. M. (Karol Marcela); Milagro-Yoldi, F.I. (Fermín Ignacio); Barajas, M. (Miguel); Dongiovanni, P. (Paola); Urtasun, R. (Raquel); Fontanellas-Romá, A. (Antonio); Longo, M. (Miriam); Sampedro, A. (Ana); Jericó-Asenjo, D. (Daniel)
    Acute intermittent porphyria (AIP) is a metabolic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, encoding the third enzyme of the heme synthesis pathway. Although AIP is characterized by low clinical penetrance (~1% of PBGD mutation carriers), patients with clinically stable disease report chronic symptoms and frequently show insulin resistance. This study aimed to evaluate the beneficial impact of nutritional interventions on correct carbohydrate dysfunctions in a mouse model of AIP that reproduces insulin resistance and altered glucose metabolism. The addition of spores of Bacillus coagulans in drinking water for 12 weeks modified the gut microbiome composition in AIP mice, ameliorated glucose tolerance and hyperinsulinemia, and stimulated fat disposal in adipose tissue. Lipid breakdown may be mediated by muscles burning energy and heat dissipation by brown adipose tissue, resulting in a loss of fatty tissue and improved lean/fat tissue ratio. Probiotic supplementation also improved muscle glucose uptake, as measured using Positron Emission Tomography (PET) analysis. In conclusion, these data provide a proof of concept that probiotics, as a dietary intervention in AIP, induce relevant changes in intestinal bacteria composition and improve glucose uptake and muscular energy utilization. Probiotics may offer a safe, efficient, and cost-effective option to manage people with insulin resistance associated with AIP.
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    18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis
    (SCHATTAUER, 2007) Marti-Climent, J.M. (Josep María); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Gavira, J.J. (Juan José); Richter, J.A. (José Ángel); Barba, J. (Joaquín); Garcia-Velloso, M. J. (María José); Ecay, M. (Margarita); Mazo, M. (Manuel); Garcia-Rodriguez, A. (Alba); Garcia-de-Jalon, J.A. (José A.); Prosper-Cardoso, F. (Felipe); Abizanda-Sarasa, G. (Gloria)
    Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.