Dieta ocidental: impacto nas lesões renais e hepáticas e no coportamento dos neutrófilos
Data
2024-07-17
Autores
Abrantes do Amaral, Mariana 
Orientadores
Olsen Saraiva Câmara, Niels
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A doença renal crônica (DRC) é caracterizada por uma diminuição progressiva da capacidade de filtração dos rins, e comprometimentos na função renal e integridade estrutural. Essa condição está se tornando cada vez mais prevalente, principalmente em sociedades ocidentais, em que mudanças nos padrões alimentares ocorreram nas últimas décadas. Pesquisas indicam que na sociedade ocidental houve o aumento do consumo de alimentos processados, ricos em açúcares e gorduras, e pobres em fibras, caracterizando esta dieta como dieta ocidental, ou Western Diet (WD). A WD, por sua vez, está associada ao aumento significativo do depósito de lipídios no corpo, o que exacerba o risco de DRC e da doença hepática gordurosa não alcoólica (DHGNA), assim como o aumento de doenças metabólicas, como obesidade e diabetes tipo 2. Esse conjunto de alterações tem criado um cenário alarmante para a saúde pública global. Dessa forma, o entendimento das vias pelas quais a WD pode levar à DRC e suas relações é de suma importância dado o novo cenário de doenças metabólicas mundial. Objetivo: O projeto buscou elucidar como a dieta ocidental pode induzir lesão renal e como essa se correlacionou à resposta inflamatória e comportamental de neutrófilos. Buscamos também entender se os mecanismos regulatórios que contribuem para a DRC estão associados à dieta ou ao crosstalk com o fígado. Métodos: Para investigar essas associações, utilizamos modelos in vivo e in silico. Larvas de zebrafish foram expostas a dietas que mimetizam a Dieta Ocidental, e avaliadas quanto a marcadores inflamatórios por PCR quantitativo, alterações metabólicas por citometria de fluxo, e padrões de migração de células imunes, particularmente neutrófilos através de microscopia confocal. Além disso, realizamos análises in silico de lesão renal e hepática observadas em humanos, de forma a fazer comparação translacional do que foi observado no modelo. Resultados: Nossas investigações revelaram que a WD de fato desencadeou lesões renais e hepáticas, acompanhadas por aumento da inflamação sistêmica, por PCR quantitativo, observamos o aumento de expressão de citocinas pró-inflamatórias, como TNF-α, IL-6, IL-1β. Como também utilizando microscopia, observamos que a dieta ocidental provoca alterações significativas no comportamento dos neutrófilos, evidenciando a relação entre comportamento dessa célula e progressão da DRC. Assim como, altera o padrão de migração de neutrófilos no rim e fígado. Nossos achados proporcionam novas interpretações sobre os mecanismos regulatórios que contribuem para a DRC e comunicação com o fígado. Além disso, as vias acionadas no modelo se correlacionam ao observado em humanos.
Introduction: Chronic kidney disease (CKD) is characterized by a progressive decrease in the kidneys' filtration capacity and impairments in renal function and structural integrity. This condition is becoming increasingly prevalent, particularly in Western societies, where changes in dietary patterns have occurred in recent decades. Research indicates that in Western society has been an increase in the consumption of processed foods, rich in sugars and fats, and low in fiber, characterizing this diet as Western Diet (WD). WD, in turn, is associated with a significant increase in lipid deposition in the body, which exacerbates the risk of CKD and non-alcoholic fatty liver disease (NAFLD). This set of changes has created an alarming scenario for global public health. Therefore, understanding the pathways through which WD can lead to CKD and their relationships is of paramount importance given the new global scenario of metabolic diseases. Objective: The project seeks to elucidate how the Western diet can induce kidney damage and how this correlates with neutrophils' inflammatory and behavioral response. We also seek to understand the regulatory mechanisms contributing to CKD associated with diet or crosstalk with the liver. Methods: We used in vivo and in silico models to investigate these associations. Zebrafish larvae were exposed to diets that mimic the Western Diet, and evaluated for inflammatory markers by quantitative PCR, metabolic changes by flow cytometry, and migration patterns of immune cells, particularly neutrophils, by microscopy. confocal. Furthermore, we performed in silico analyses of kidney and liver injury observed in humans, to make a translational comparison of what was observed in the model. Results: Our investigations revealed that WD triggered kidney and liver injuries, accompanied by increased systemic inflammation. Using quantitative PCR, we observed an increase in the expression of proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β. Using microscopy, we also observed that the Western diet causes significant changes in the behavior of neutrophils, highlighting the relationship between neutrophil behavior and the progression of CKD. WD also changes the neutrophil migration pattern in the kidney and liver. Our findings provide new interpretations of the regulatory mechanisms contributing to CKD and liver communication. Furthermore, the pathways activated in the model correlate with what is observed in humans.
Introduction: Chronic kidney disease (CKD) is characterized by a progressive decrease in the kidneys' filtration capacity and impairments in renal function and structural integrity. This condition is becoming increasingly prevalent, particularly in Western societies, where changes in dietary patterns have occurred in recent decades. Research indicates that in Western society has been an increase in the consumption of processed foods, rich in sugars and fats, and low in fiber, characterizing this diet as Western Diet (WD). WD, in turn, is associated with a significant increase in lipid deposition in the body, which exacerbates the risk of CKD and non-alcoholic fatty liver disease (NAFLD). This set of changes has created an alarming scenario for global public health. Therefore, understanding the pathways through which WD can lead to CKD and their relationships is of paramount importance given the new global scenario of metabolic diseases. Objective: The project seeks to elucidate how the Western diet can induce kidney damage and how this correlates with neutrophils' inflammatory and behavioral response. We also seek to understand the regulatory mechanisms contributing to CKD associated with diet or crosstalk with the liver. Methods: We used in vivo and in silico models to investigate these associations. Zebrafish larvae were exposed to diets that mimic the Western Diet, and evaluated for inflammatory markers by quantitative PCR, metabolic changes by flow cytometry, and migration patterns of immune cells, particularly neutrophils, by microscopy. confocal. Furthermore, we performed in silico analyses of kidney and liver injury observed in humans, to make a translational comparison of what was observed in the model. Results: Our investigations revealed that WD triggered kidney and liver injuries, accompanied by increased systemic inflammation. Using quantitative PCR, we observed an increase in the expression of proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β. Using microscopy, we also observed that the Western diet causes significant changes in the behavior of neutrophils, highlighting the relationship between neutrophil behavior and the progression of CKD. WD also changes the neutrophil migration pattern in the kidney and liver. Our findings provide new interpretations of the regulatory mechanisms contributing to CKD and liver communication. Furthermore, the pathways activated in the model correlate with what is observed in humans.
Descrição
Citação
AMARAL, Mariana Abrantes do. Dieta ocidental: impacto nas lesões renais e hepáticas e no coportamento dos neutrófilos. São Paulo. 2024. Tese (Doutorado em Medicina: nefrologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2024.