Publication: Papel de la lipotoxicidad y la disfunción mitocondrial en las alteraciones cardiacas y metabólicas asociadas a la obesidad
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2019-02-25
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Universidad Complutense de Madrid
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Abstract
La obesidad se define como una excesiva acumulación de grasa debido a undesequilibrio entre las calorías consumidas y gastadas. La obesidad mundial ha crecido dramáticamente en las últimas décadas por lo que no es sorprendente que numerosos estudios se hayan llevado a cabo para investigar su efecto dañino sobre la salud humana.Una de las características de los pacientes obesos es la presencia de adipocitos más grandes los cuáles una vez alcanzado su límite de expansión tienen una menor capacidad de almacenamiento de grasa dando lugar a un aumento de los niveles de ácidos grasos circulantes los cuales se pueden depositar en tejidos no adiposos, incluido el corazón, ejerciendo efectos tóxicos en los mismos. Además, la obesidad se asocia con alteraciones estructurales y funcionales en el corazón las cuales pueden dar lugar a disfunción cardiaca. De hecho, las enfermedades cardiovasculares son la primera causa de muerte en individuos con obesidad o diabetes. Entre los mecanismos que contribuyen a la aparición de alteraciones estructurales y funcionales se encuentran la lipotoxicidad cardiaca, las alteraciones en el uso de sustratos metabólicos, mediadores profibróticos como Galectina 3 (Gal-3), la disfunción mitocondrial y el estrés oxidativo, los cuales facilitan el desarrollo de fibrosis cardiaca con consecuencias funcionales. Niveles patológicos de especies reactivas de oxígeno siendo la mitocondria la principal fuente de los mismos, se ha demostrado que tienen un efecto dañino en el corazón...
Obesity is defined as an abnormal or excessive fat accumulation due to an energy imbalance between calories consumed and expended. Worldwide obesity has grown dramatically in the last decades so it is not surprising that numerous studies have been performed to investigate its harmful effect on human health. One of the characteristics of obese patients is the presence of larger adipocytes which reach a limit and have diminished capacity to store fat, thereby leading to elevation of circulating fatty acids which can deposit in non-adipose tissues, including the heart,exerting toxic effects. Moreover, obesity is associated with structural and functional alterations in the heart that can lead to cardiac dysfunction. In fact, cardiovascular disease is the primary cause of death in individuals with obesity and diabetes. Among the mechanisms that contribute to cardiac structural and functional alterations, cardiac lipotoxicity, alterations in the use of metabolic substrates, profibrotic mediators such as Galectin-3 (Gal-3), mitochondrial dysfunction and oxidative stress are some of these which facilitate the development of cardiac fibrosis with functional consequences. Pathological ROS levels have been demonstrated to have harmful effects in the heart, with the mitochondria being the main source of ROS. Moreover, oxidative stress can also participate in the adipose tissue remodelling which can be underlying metabolic alterations associated with obesity...
Obesity is defined as an abnormal or excessive fat accumulation due to an energy imbalance between calories consumed and expended. Worldwide obesity has grown dramatically in the last decades so it is not surprising that numerous studies have been performed to investigate its harmful effect on human health. One of the characteristics of obese patients is the presence of larger adipocytes which reach a limit and have diminished capacity to store fat, thereby leading to elevation of circulating fatty acids which can deposit in non-adipose tissues, including the heart,exerting toxic effects. Moreover, obesity is associated with structural and functional alterations in the heart that can lead to cardiac dysfunction. In fact, cardiovascular disease is the primary cause of death in individuals with obesity and diabetes. Among the mechanisms that contribute to cardiac structural and functional alterations, cardiac lipotoxicity, alterations in the use of metabolic substrates, profibrotic mediators such as Galectin-3 (Gal-3), mitochondrial dysfunction and oxidative stress are some of these which facilitate the development of cardiac fibrosis with functional consequences. Pathological ROS levels have been demonstrated to have harmful effects in the heart, with the mitochondria being the main source of ROS. Moreover, oxidative stress can also participate in the adipose tissue remodelling which can be underlying metabolic alterations associated with obesity...
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Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Fisiología, leída el 20-11-2018