Efectos de la dieta de cafetería y del consumo voluntario de alcohol en la expresión de genes relacionados con plasticidad neuronal en el sistema de recompensa
Fecha
2023
Tipo
tesis de maestría
Autores
Castro Murillo, Maripaz
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Resumen
El aumento de la obesidad a nivel global y regional representa un problema de salud pública, dadas las complicaciones crónicas asociadas a esta condición. La obesidad es un rasgo complejo en el que intervienen factores genéticos y ambientales. Entre los factores de riesgo asociados a obesidad se encuentra el cambio en los patrones alimentarios de la sociedad occidental, caracterizado principalmente por el aumento en el consumo y disponibilidad de alimentos con un alto contenido energético, grasa y azúcar. Además, se ha sugerido que el incremento en el consumo de alcohol contribuye con el aumento en las cifras de obesidad, por lo que este factor debería ser tomado en cuenta en estudios de obesidad tanto a nivel preclínico como epidemiológico. En esta tesis implementamos un modelo preclínico de obesidad para estudiar los efectos independientes y la interacción entre una dieta altamente palatable y energéticamente densa típica de las sociedades occidentales conocida como dieta de cafetería (CAF) y el consumo voluntario de etanol (ALC) sobre los parámetros biométricos, nutricionales, conductuales y neuroquímicos (expresión de genes y proteínas) implicados en la plasticidad neuronal en varias regiones cerebrales del sistema de recompensa. Siguiendo un diseño factorial de 2x2, se expuso a 50 ratas Wistar macho durante 9 semanas a la combinación de los siguientes factores: Dieta (dieta estándar vs. CAF) y Etanol (agua vs. ALC). La ingesta de alimentos y el peso corporal se midieron diariamente, mientras que los efectos conductuales se evaluaron en la prueba de campo abierto (OFT) al finalizar la exposición a los tratamientos. Finalmente, se eutanasiaron los animales, se disecaron los cerebros y se analizaron los genes y proteínas en regiones del sistema de recompensa como la corteza prefrontal medial (CPFm), el núcleo accumbens (NAc), el estriado dorsal (ED) y el hipocampo (HPC). Los resultados mostraron que la CAF causó hiperfagia, aumentó el peso corporal y la acumulación de grasa perigonadal y abdominal, mientras que el ALC solo incrementó la grasa de la zona abdominal. A nivel conductual, la CAF, y en menor medida el ALC, indujeron un efecto de tipo ansiolítico sin afectar la actividad psicomotora general. A nivel cerebral, la CAF y el ALC tuvieron efectos independientes y de interacción sobre la expresión génica y los niveles de proteínas. La CAF indujo un incremento de los niveles de ARNm de CREB en el HPC y una disminución en la CPFm. El ALC, por el contrario, reguló negativamente la expresión de CREB, CRFR1 y TrkB en el HPC. En cuanto al contenido de proteínas, ambos tratamientos redujeron en la misma proporción la proteína CREB en el ED. Sin embargo, el ALC, y en menor medida la CAF, aumentaron la relación pCREB/CREB en la CPFm y el ED. Considerando las diferencias observadas en los niveles de ARNm y proteína, el parámetro más sensible a ambos tratamientos fue CREB, y en segundo lugar, la expresión de CRFR1. Nuestros hallazgos sugieren que nuestro modelo es útil y robusto para estudiar los efectos neuroconductuales de una dieta occidentalizada moderna en el desarrollo de trastornos metabólicos y obesidad.
The increase in global and regional obesity represents a public health problem, given the chronic complications associated with this condition. Obesity is a complex trait influenced by genetic and environmental factors. The change in dietary patterns in Western society is among the risk factors associated with obesity, which are characterized mainly by an increase in the consumption and availability of high-energy, fatty, and sugary foods. Additionally, it has been suggested that increased alcohol consumption contributes to the rising rates of obesity, so this factor should be considered in both preclinical and epidemiological obesity studies. In the present thesis, we implemented a preclinical model of obesity to study the independent and interactive effects of a highly palatable and energetically dense diet typical of Western societies –known as cafeteria diet (CAF)– and voluntary ethanol consumption (ALC), on obesity-related biometric, nutritional, behavioral, and neurochemical parameters. Fifty male Wistar rats were exposed for 9 weeks to the combination of Diet (standard vs. CAF) and Alcohol (water vs. ALC) factors. Food intake and body weight were scored daily, whereas the behavioral effects were assessed after the nine-weeks period. Gene expression and protein levels were analyzed in brain regions of the reward system such as the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsal striatum (DS), and the hippocampus (HPC). We found that CAF caused hyperphagia, body weight gain, and body fat accumulation, while both treatments increased abdominal fat. In the open-field test, CAF, and to a lesser extent ALC, induced an anxiolytic-like effect. At the brain level, CAF changed CREB expression in opposite directions between the mPFC and the HPC, decreasing and increasing it, respectively. ALC, in contrast, downregulated CREB, CRFR1, and TrkB expression in the HPC. Both treatments equally reduced CREB protein in the DS. ALC, and to a lesser extent CAF, increased the pCREB/CREB ratio in the mPFC and the DS. Altogether, CREB and CRFR1 were the most sensitive genes to the treatments. Our preclinical model proved to be useful for studying the neurobehavioral effects of a modern Westernized diet and alcohol consumption on the risk of suffering metabolic disorders and obesity.
The increase in global and regional obesity represents a public health problem, given the chronic complications associated with this condition. Obesity is a complex trait influenced by genetic and environmental factors. The change in dietary patterns in Western society is among the risk factors associated with obesity, which are characterized mainly by an increase in the consumption and availability of high-energy, fatty, and sugary foods. Additionally, it has been suggested that increased alcohol consumption contributes to the rising rates of obesity, so this factor should be considered in both preclinical and epidemiological obesity studies. In the present thesis, we implemented a preclinical model of obesity to study the independent and interactive effects of a highly palatable and energetically dense diet typical of Western societies –known as cafeteria diet (CAF)– and voluntary ethanol consumption (ALC), on obesity-related biometric, nutritional, behavioral, and neurochemical parameters. Fifty male Wistar rats were exposed for 9 weeks to the combination of Diet (standard vs. CAF) and Alcohol (water vs. ALC) factors. Food intake and body weight were scored daily, whereas the behavioral effects were assessed after the nine-weeks period. Gene expression and protein levels were analyzed in brain regions of the reward system such as the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsal striatum (DS), and the hippocampus (HPC). We found that CAF caused hyperphagia, body weight gain, and body fat accumulation, while both treatments increased abdominal fat. In the open-field test, CAF, and to a lesser extent ALC, induced an anxiolytic-like effect. At the brain level, CAF changed CREB expression in opposite directions between the mPFC and the HPC, decreasing and increasing it, respectively. ALC, in contrast, downregulated CREB, CRFR1, and TrkB expression in the HPC. Both treatments equally reduced CREB protein in the DS. ALC, and to a lesser extent CAF, increased the pCREB/CREB ratio in the mPFC and the DS. Altogether, CREB and CRFR1 were the most sensitive genes to the treatments. Our preclinical model proved to be useful for studying the neurobehavioral effects of a modern Westernized diet and alcohol consumption on the risk of suffering metabolic disorders and obesity.
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Palabras clave
Neuroplasticidad, Alimentos altamente palatables, Sobreingesta, Dopamina, Modelos animales