Person: Hurtado Carneiro, Verónica
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First Name
Verónica
Last Name
Hurtado Carneiro
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Fisiología
Area
Fisiología
Identifiers
12 results
Search Results
Now showing 1 - 10 of 12
Item High-fat diet alters PAS kinase regulation by fasting and feeding in liver(The Journal of Nutritional Biochemistry, 2018) Pérez García, Ana; Dongil, Pilar; Hurtado Carneiro, Verónica; Blázquez Fernández, Enrique; Sanz Miguel, María Del Carmen; Álvarez García, ElviraThe prevalence of overweight and obesity in the population, along with their associated complications, is a major factor contributing to increased morbidity and mortality in developed countries. The liver is a vital organ for maintaining metabolic homeostasis, especially in the adjustment periods in fasting and feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy metabolism in response to nutritional status. PASK-deficient mice with a high-fat diet (HFD) resist the development of obesity and hepatic steatosis, with improved insulin sensitivity. We have investigated the regulation of the PASK expression in an HFD, as well as its role in adapting to fasting and feeding conditions. PASK-deficient mice with an HFD record improved parameters for the following: body weight, glucose tolerance, insulin resistance and serum lipid parameters. An HFD alters the down-regulation of Pask expression produced by fasting, as normally happens in a standard-fat diet. PASK deficiency blocks or diminishes the expression of many genes overexpressed in HFD-fed mice, such as the following: transcription factors involved in the regulation of gluconeogenic enzymes, the transport of fatty acid into mitochondria, beta-oxidation and de novo lipogenesis. PASK also regulates gene expression posttranscriptionally through the short noncoding RNAs involved in lipid metabolism and glucose homeostasis. The expression of miR-33a and miR-143 changes in PASK-deficient mice with an HFD. Thus, PASK-deficient mice improved their adaptation to feeding/fasting through a highly regulated molecular mechanism that controls the expression and function of the transcription factors, enzymes and miRNAs involved in glucose and insulin signaling.Item PAS Kinase Is a Nutrient and Energy Sensor in Hypothalamic Areas Required for the Normal Function of AMPK and mTOR/S6K1(Molecular Neurobiology, 2014) Hurtado Carneiro, Verónica; Roncero Rincón, Isabel; Egger, Sascha S.; Wenger, Roland H.; Blázquez Fernández, Enrique; Sanz Miguel, María Del Carmen; Álvarez García, Elvira; Bazán, Nicolas G.The complications caused by overweight, obesity and type 2 diabetes are one of the main problems that increase morbidity and mortality in developed countries. Hypothalamic metabolic sensors play an important role in the control of feeding and energy homeostasis. PAS kinase (PASK) is a nutrient sensor proposed as a regulator of glucose metabolism and cellular energy. The role of PASK might be similar to other known metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). PASK-deficient mice resist diet-induced obesity. We have recently reported that AMPK and mTOR/S6K1 pathways are regulated in the ventromedial and lateral hypothalamus in response to nutritional states, being modulated by anorexigenic glucagon-like peptide-1 (GLP-1)/exendin-4 in lean and obese rats. We identified PASK in hypothalamic areas, and its expression was regulated under fasting/re-feeding conditions and modulated by exendin-4. Furthermore, PASK-deficient mice have an impaired activation response of AMPK and mTOR/S6K1 pathways. Thus, hypothalamic AMPK and S6K1 were highly activated under fasted/re-fed conditions. Additionally, in this study, we have observed that the exendin-4 regulatory effect in the activity of metabolic sensors was lost in PASK-deficient mice, and the anorexigenic properties of exendin-4 were significantly reduced, suggesting that PASK could be a mediator in the GLP-1 signalling pathway. Our data indicated that the PASK function could be critical for preserving the nutrient effect on AMPK and mTOR/S6K1 pathways and maintain the regulatory role of exendin-4 in food intake. Some of the antidiabetogenic effects of exendin-4 might be modulated through these processes.- Project number: 48
Item Elaboración de blogs como herramienta virtual de aprendizaje y trabajo en equipo(2017) Sanz Miguel, María Del Carmen; Martínez Mora, María Del Carmen; Giné Domínguez, Elena; López Moreno, José Antonio; Hurtado Carneiro, Verónica; Lamana Rodríguez, Amalia; Valiño Seoane, Iria; Triguero Martínez, AnaEste proyecto de innovación se enmarca dentro de las actividades académicas no presenciales. Se trata de la elaboración de blogs como herramienta virtual de aprendizaje. Los blogs son un recurso de aprendizaje individual o grupal, de gran versatilidad y dinamización del aula. Además, promueve el desarrollo de competencias generales, específicas y transversales que los alumnos deben adquirir durante su formación. Creemos que su aplicación es especialmente interesante en asignaturas como “Bases Celulares de la Genética Humana” impartida en primero de Medicina, donde los alumnos se encuentran con una dificultad añadida a la complejidad de sus fundamentos: unos conceptos complejos con una terminología muy específica para asimilarlos. Los futuros médicos deberán ser capaces, de explicar con un lenguaje sencillo y comprensible a los pacientes la implicación de la genética en las patologías. Consideramos que el uso de blogs está especialmente indicado en este caso para facilitar la adquisición de esta competencia específica, además de apoyar el aprendizaje de parte de los contenidos de la asignatura y promover el trabajo en equipo. Esta herramienta aporta a los alumnos las competencias necesarias para su formación integral como profesional de la salud promoviendo el intercambio colaborativo. Es además, un recurso que puede ser utilizado tanto para la evaluación continua, por parte del profesor durante y a la finalización del diseño del blog, así como para la coevaluación entre los alumnos. Por tanto, esta propuesta facilita el aprendizaje creando espacios para ello. En definitiva, crea oportunidades de aprendizaje. Item Sensores metabólicos en el cerebro: intercomunicación con los péptidos reguladores de la ingesta de alimentos(2015) Hurtado Carneiro, Verónica; Álvarez García, Elvira; Sanz Miguel, María del Carmen- Project number: PIMCD207
Item Desarrollo e implementación de una herramienta de evaluación en los tribunales de los Trabajos de Fin de Grado y Fin de Máster en las ciencias de la salud(2016) Sanz Miguel, María Del Carmen; Giné Domínguez, Elena; Navas Hernández, María Ángeles; Hurtado Carneiro, Verónica; Benito Miguel, Marta; Gutiérrez Nogués, Ángel; Dongil Sánchez, Pilar; Pérez García, Ana Item Glucagon-Like Peptide 1 (GLP-1) Can Reverse AMP-Activated Protein Kinase (AMPK) and S6 Kinase (P70S6K) Activities Induced by Fluctuations in Glucose Levels in Hypothalamic Areas Involved in Feeding Behaviour(Molecular Neurobiology, 2012) Hurtado Carneiro, Verónica; Sanz Miguel, María Del Carmen; Roncero Rincón, Isabel; Vázquez Pérez, Patricia; Blázquez Fernández, Enrique; Álvarez García, Elvira; Rancán, Lisa; Bazán, Nicolas G.The anorexigenic peptide, glucagon-like peptide-1 (GLP-1), reduces glucose metabolism in the human hypothalamus and brain stem. The brain activity of metabolic sensors such as AMP-activated protein kinase (AMPK) responds to changes in glucose levels. The mammalian target of rapamycin (mTOR) and its downstream target, p70S6 kinase (p70S6K), integrate nutrient and hormonal signals. The hypothalamic mTOR/p70S6K pathway has been implicated in the control of feeding and the regulation of energy balances. Therefore, we investigated the coordinated effects of glucose and GLP-1 on the expression and activity of AMPK and p70S6K in the areas involved in the control of feeding. The effect of GLP-1 on the expression and activities of AMPK and p70S6K was studied in hypothalamic slice explants exposed to low- and high-glucose concentrations by quantitative real-time RT-PCR and by the quantification of active-phosphorylated protein levels by immunoblot. In vivo, the effects of exendin-4 on hypothalamic AMPK and p70S6K activation were analysed in male obese Zucker and lean controls 1 h after exendin-4 injection to rats fasted for 48 h or after re-feeding for 2–4 h. High-glucose levels decreased the expression of Ampk in the lateral hypothalamus and treatment with GLP-1 reversed this effect. GLP-1 treatment inhibited the activities of AMPK and p70S6K when the activation of these protein kinases was maximum in both the ventromedial and lateral hypothalamic areas. Furthermore, in vivo s.c. administration of exendin-4 modulated AMPK and p70S6K activities in those areas, in both fasted and re-fed obese Zucker and lean control rats.Item Insulin-Receptor Substrate-2 (IRS-2) Is Required for Maintaining Glucokinase and Glucokinase Regulatory Protein Expression in Mouse Liver(Plos One, 2013) Roncero Rincón, Isabel; Álvarez García, Elvira; Acosta, Carlos; Sanz Miguel, María Del Carmen; Barrio, Pedro; Hurtado Carneiro, Verónica; Burks, Deborah; Blázquez Fernández, Enrique; Hennige, Anita MagdalenaInsulin receptor substrate (IRS) proteins play important roles in hepatic nutrient homeostasis. Since glucokinase (GK) and glucokinase regulatory protein (GKRP) function as key glucose sensors, we have investigated the expression of GK and GKRP in liver of Irs-2 deficient mice and Irs2(-/-) mice where Irs2 was reintroduced specifically into pancreatic β-cells [RIP-Irs-2/IRS-2(-/-)]. We observed that liver GK activity was significantly lower (p<0.0001) in IRS-2(-/-) mice. However, in RIP-Irs-2/IRS-2(-/-) mice, GK activity was similar to the values observed in wild-type animals. GK activity in hypothalamus was not altered in IRS-2(-/-) mice. GK and GKRP mRNA levels in liver of IRS-2(-/-) were significantly lower, whereas in RIP-Irs-2/IRS-2(-/-) mice, both GK and GKRP mRNAs levels were comparable to wild-type animals. At the protein level, the liver content of GK was reduced in IRS-2(-/-) mice as compared with controls, although GKRP levels were similar between these experimental models. Both GK and GKRP levels were lower in RIP-Irs-2/IRS-2(-/-) mice. These results suggest that IRS-2 signalling is important for maintaining the activity of liver GK. Moreover, the differences between liver and brain GK may be explained by the fact that expression of hepatic, but not brain, GK is controlled by insulin. GK activity was restored by the β-cell compensation in the RIP-Irs-2/IRS-2 mice. Interestingly, GK and GKRP protein expression remained low in RIP-Irs-2/IRS-2(-/-) mice, perhaps reflecting different mRNA half-lives or alterations in the process of translation and post-translational regulation.Item Glucokinase as a glucose sensor in hypothalamus. Regulation by orexigenic and anorexigenic peptides(Update on Mechanisms of Hormone Action - Focus on Metabolism, Growth and Reproduction, 2011) Sanz Miguel, María Del Carmen; Roncero Rincón, Isabel; Álvarez García, Elvira; Hurtado Carneiro, Verónica; Blázquez Fernández, Enrique; Aimaretti, Gianluca; Marzullo, Paolo; Prodam, FlaviaItem Pas Kinase Deficiency Triggers Antioxidant Mechanisms in the Liver(Scientific Reports, 2018) Dongil, Pilar; Pérez García, Ana; Hurtado Carneiro, Verónica; Herrero de Dios, Carmen; Blázquez Fernández, Enrique; Álvarez García, Elvira; Sanz Miguel, María Del CarmenMetabolic dysfunction in the liver is the cause of numerous pathologies, which are associated with an altered redox state. PASK (PAS Domain Kinase) is a nutrient and bioenergetic sensor. We contend that PASK could act as an oxidative stress sensor in liver and/or control the metabolic balance, playing a role in the mitochondrial homeostasis. Using PASK-deficient mice, we observed that PASK deficiency promotes antioxidant response mechanisms: a lower production of ROS/RNS under non-fasting conditions, overexpression of genes coding to ROS-detoxifying enzymes and mitochondrial fusion proteins (MnSod Gpx, Mfn1 and Opa1), coactivator Ppargc1a, transcription factors (Pparg and FoxO3a) and deacetylase Sirt1. Also, under fasting conditions, PASK deficiency induced the overexpression of Ppargc1a, Ppara, Pparg, FoxO3a and Nrf2 leading to the overexpression of genes coding to antioxidant enzymes such as MnSOD, Cu/ZnSOD, GPx, HO1 and GCLm. Additionally, inducing PINK1 involved in cell survival and mitophagy. These changes kept ROS steady levels and improved the regenerative state. We suggest a new role for PASK as a controller of oxidative stress and mitochondrial dynamics in the liver. In fact, antioxidant response is PASK dependent. PASK-targeting could therefore be a good way of reducing the oxidative stress in order to prevent or treat liver diseases.Item PAS Kinase as a Nutrient Sensor in Neuroblastoma and Hypothalamic Cells Required for the Normal Expression and Activity of Other Cellular Nutrient and Energy Sensors(Molecular Neurobiology, 2013) Hurtado Carneiro, Verónica; Roncero Rincón, Isabel; Blázquez Fernández, Enrique; Álvarez García, Elvira; Sanz Miguel, María Del Carmen; Bazán, Nicolas G.PAS kinase (PASK) is a nutrient sensor that is highly conserved throughout evolution. PASK-deficient mice reveal a metabolic phenotype similar to that described in S6 kinase-1 S6K1-deficient mice that are protected against obesity. Hypothalamic metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR), play an important role in feeding behavior, the homeostasis of body weight, and energy balance. These sensors respond to changes in nutrient levels in the hypothalamic areas involved in feeding behavior and in neuroblastoma N2A cells, and we have recently reported that those effects are modulated by the anorexigenic peptide glucagon-like peptide-1 (GLP-1). Here, we identified PASK in both N2A cells and rat VMH and LH areas and found that its expression is regulated by glucose and GLP-1. High levels of glucose decreased Pask gene expression. Furthermore, PASK-silenced N2A cells record an impaired response by the AMPK and mTOR/S6K1 pathways to changes in glucose levels. Likewise, GLP-1 effect on the activity of AMPK, S6K1, and other intermediaries of both pathways and the regulatory role at the level of gene expression were also blocked in PASK-silenced cells. The absence of response to low glucose concentrations in PASK-silenced cells correlates with increased ATP content, low expression of mRNA coding for AMPK upstream kinase LKB1, and enhanced activation of S6K1. Our findings indicate that, at least in N2A cells, PASK is a key kinase in GLP-1 actions and exerts a coordinated response with the other metabolic sensors, suggesting that PASK might play an important role in feeding behavior.