GIUV2022-534
The acquisition of sedentary lifestyles that promote obesity and aging in the population have increased the incidence of metabolic disorders. Thus, type 2 diabetes mellitus (T2DM), whose main characteristic is insulin resistance (IR), has increased exponentially in recent decades. In addition, IR is usually accompanied by adipose tissue dysfunction, dyslipidemia and hypertension, metabolic disorders that together are called metabolic syndrome and that, furthermore, are increasingly observed in patients with type 1 diabetes mellitus (T1DM). The most important complications of this syndrome are cardiovascular disease (CVD), whose most frequent underlying cause is atherosclerosis, and non-alcoholic fatty liver disease (NAFLD), an asymptomatic disease that can progress to more serious forms such as non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Due to the increase in prevalence and severity, these diseases will present an important contribution to morbidity and mortality and a socioeconomic challenge in the near future. Therefore, it is of great relevance to investigate the common molecular mechanisms that connect these pathologies to effectively reduce their...The acquisition of sedentary lifestyles that promote obesity and aging in the population have increased the incidence of metabolic disorders. Thus, type 2 diabetes mellitus (T2DM), whose main characteristic is insulin resistance (IR), has increased exponentially in recent decades. In addition, IR is usually accompanied by adipose tissue dysfunction, dyslipidemia and hypertension, metabolic disorders that together are called metabolic syndrome and that, furthermore, are increasingly observed in patients with type 1 diabetes mellitus (T1DM). The most important complications of this syndrome are cardiovascular disease (CVD), whose most frequent underlying cause is atherosclerosis, and non-alcoholic fatty liver disease (NAFLD), an asymptomatic disease that can progress to more serious forms such as non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Due to the increase in prevalence and severity, these diseases will present an important contribution to morbidity and mortality and a socioeconomic challenge in the near future. Therefore, it is of great relevance to investigate the common molecular mechanisms that connect these pathologies to effectively reduce their incidence and associated morbidity. The group's research activity focuses on the search for and description of new genes and signalling pathways of one of the most important molecular mechanisms that connects these metabolic pathologies to the development of a chronic inflammatory state caused by a maladjustment of the immune system. Thus, the release of inflammatory mediators from dysfunctional adipose tissue could provoke the evolution of NAFLD to more severe stages of NAFLD-HCC. This tissue dysfunction can also produce an imbalance of immune cells, contributing to the generation of unstable atherosclerotic plaques that are the precursor to ischemic and/or thromboembolic vascular phenomena. Significantly, the most effective current treatments are based on the reduction of risk factors that predispose individuals to these pathologies such as lifestyle changes (weight loss, physical exercise), the control of blood glucose and dyslipidemia and the use of antihypertensives and anticoagulants. This is why the research group's activity represents a new perspective within the new paradigm in the study of metabolic disease by focusing on understanding the mechanisms that operate within already damaged tissue rather than on the preventive modulation of risk factors that promote damage. Specifically, it aims to: 1) study and characterise immune cells in damaged tissue and identify key proteins that modulate the balance of these cells; 2) study cellular plasticity that promotes the progression of damage triggered by inflammatory processes; 3) identify possible therapeutic targets that reverse tissue damage. To carry out this activity, the group makes use of cellular models and murine experimental models of disease. Thus, it uses mice deficient in the apolipoprotein E gene or the low-density lipoprotein receptor (LDLR) gene, which develop hypercholesterolemia and atherosclerosis; mice deficient in the insulin receptor 2 substrate that have DMT2 and RI; and mice subjected to different types of diets with variable cholesterol and fat content. In addition, these genetic deficiencies and treatments are combined with gain- and loss-of-function strategies of other genes that, based on previous studies and new hypotheses, may potentially be regulators of systemic and tissue inflammatory processes.
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- Describir nuevos mecanismos moleculares clave en el desarrollo de patologias asociadas al desajuste metabolico
- Describir nuevos mecanismos que favorecen el avance de la enfermedad del higado graso en la resistencia a la insulina
- Describir mecanismos moleculares relacionadas con el sistema inmune y la inflamacion en el desarrollo de la aterosclerosis
- Identificar dianas terapeuticas para el tratamiento de las enfermedades metabolicas
- Identify new inflammatory molecular mechanisms and therapeutic targets for the treatment of fatty liver disease.Study using animal models that develop fatty liver provoked by a diet high in sugar, fat and cholesterol, as well as the role of genes in the modulation of immune cells. For this purpose, loss/gain-of-function strategies and transcriptomic and proteomic methodologies are used.
- Characterization of new molecular mechanisms of the cellular plasticity associated with the development of atherosclerosis.Identification of new inflammatory signalling pathways that modulate vascular smooth muscle cell plasticity (VSMCs) in the formation of vulnerable atheroma plaques in models of atherosclerosis. To this end, cell tracing and bone marrow replacement experiments are carried out.
| Name | Nature of participation | Entity | Description |
|---|---|---|---|
| HERMINIA GONZALEZ NAVARRO | Director | Universitat de València | |
| Research team | |||
| ELENA JIMENEZ MARTI | Member | Universitat de València | |
| MARÍA AGUILAR BALLESTER | Collaborator | FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNIDAD VALENCIANA (FUNDACION INCLIVA) | researcher |
| Marta Ruiz Piquer | Collaborator | FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNIDAD VALENCIANA (FUNDACION INCLIVA) | technical officer |
| Pablo Arjona Fernández-Sanabria | Collaborator | FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNIDAD VALENCIANA (FUNDACION INCLIVA) | graduate |
| GEMA HURTADO GENOVÉS | Collaborator | FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNIDAD VALENCIANA (FUNDACION INCLIVA) | researcher |
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- hígado graso no alcohólico; inflamación; mRNAseq; modelos animales; dieta rica en grasa;
- aterosclerosis; plasticidad celular; transcriptómica;
