http://www.bdtd.uerj.br/handle/1/3533 2026-04-12T02:22:56Z http://www.bdtd.uerj.br/handle/1/24795 Título: Influência do excesso de frutose e lipídio dietéticos, isolados ou em associação, na disfunção do tecido adiposo marrom Autor: Glauser, Jade Sancha de Oliveira Primeiro orientador: Souza-Mello, Vanessa de Abstract: Obesity causes morphological and metabolic changes in brown adipocytes, causing dysfunction, known as whitening. A high-calorie diet is constantly associated with the phenomenon, but the influence of carbohydrates and lipids as energy substrates in this process has not yet been explored. This study investigated the effects of a comparable dietary excess of fat or fructose and their combination on interscapular brown adipose tissue (iBAT) whitening and markers of mitochondrial dynamics in a diet-induced obesity murine model. Male C57BL/6 adult mice were randomly assigned into four groups according to the diet: control diet (C, following AIN-93M), high-fat diet (HF, 32% energy as lard), high-fructose diet (HFRU, 32% energy as fructose) or for high-fat/high- fructose diet (HF-HFRU, 32% as lard and 32% as fructose) for 12 weeks. All diets caused insulin resistance and iBAT whitening, albeit with overweight only in the HF and HF-HFRU groups. Principal Component Analysis (PCA) indicated that the HFRU scored loaded next to inflammation markers, and the HF diet influenced more mitochondrial genes. However, iBAT whitening in all groups was associated with deficits in mitochondrial dynamics and vascularization. Similar increases in dietary saturated fat or fructose (32% as energy) and their combination caused insulin resistance and brown adipocyte dysfunction (whitening) independent of being overweight. In comparison, the PC scores of the HFRU groups were closer to the HF- HFRU group than the HF group, implying a worse outcome and highlighting the importance of limiting saturated fat and fructose intake from ultra-processed foods. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação 2025-02-19T00:00:00Z http://www.bdtd.uerj.br/handle/1/24518 Título: Treinamento Contínuo de Intensidade Moderada e Treinamento Intervalado de Alta Intensidade: Prevenção da obesidade por modulação do eixo intestino-adiposo Autor: Oliveira, Daiana Araujo de Santana Primeiro orientador: Souza-Mello, Vanessa Abstract: Excessive consumption of saturated fat disrupts energy homeostasis and is associated with increased adiposity, insulin resistance, low-grade inflammation, dysfunction of adipose tissue (AT), reduced thermogenesis, and alterations in gut microbiota composition. Intestinal dysbiosis, in turn, impairs non-shivering thermogenesis (NST), especially in the context of obesity. Evidence suggests that the anti-obesogenic effects of physical exercise involve modulation of the gut microbiota, induction of thermogenesis in white adipose tissue (WAT), and suppression of inflammatory signals directed at brown adipose tissue (BAT). This study investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the prevention of overweight and metabolic alterations in male C57BL/6 mice (3 months old) fed a high-fat diet (HFD). Animals were divided into six experimental groups (n = 10 per group): control diet (C), C + HIIT, C + MICT, high-fat diet (HF), HF + HIIT, and HF + MICT. Exercise protocols were applied over ten weeks. The results showed that both HIIT and MICT restored body mass, attenuated glucose intolerance, and prevented hyperinsulinemia in the HFD-fed groups. The HF diet induced gut dysbiosis and increased intestinal permeability, while both exercise protocols preserved microbial diversity and the expression of tight junction (TJ) genes such as Zo-1 and Jam-a. The HF-HIIT and HF-MICT groups exhibited lower plasma LPS concentrations, reduced activation of the Lbp–Cd14–Tlr4 inflammatory pathway in BAT, and downregulation of Nlrp3 and Il1β, indicating preservation of adaptive thermogenesis. Furthermore, both protocols improved the expression of genes related to mitochondrial dynamics, resulting in sustained expression of thermogenic markers both dependent and independent of UCP1, as well as maintenance of the beige phenotype in subcutaneous WAT (scWAT). HIIT, in particular, promoted more pronounced anti-inflammatory effects, with sustained thermogenesis even with 78% less distance covered compared to MICT. In conclusion, both HIIT and MICT were effective in preventing the deleterious metabolic effects induced by a high-fat diet, primarily by modulating gut microbiota and suppressing inflammatory signals along the gut–adipose tissue axis. HIIT demonstrated greater metabolic efficiency and a more robust anti-obesogenic effect, standing out as a promising strategy for the prevention and management of diet-induced obesity. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2025-07-01T00:00:00Z http://www.bdtd.uerj.br/handle/1/24420 Título: Associações genéticas como fatores de risco para narcolepsia em pacientes atendidos no Hospital Universitário Pedro Ernesto Autor: Mendes-Oliveira, Victoria Primeiro orientador: Porto, Luis Cristóvão de Moraes Sobrino Abstract: Narcolepsy is a chronic disorder characterized by excessive daytime sleepiness, classified into narcolepsy type 1 (NT1) and type 2 (NT2). Individuals with NT1 present hypocretin deficiency and cataplexy, while NT2 maintains normal hypocretin levels and lacks cataplexy. NT1 is strongly associated with the HLA-DQB1*06:02 allele, a relevant genetic marker for diagnosis, and has other immunogenetic associations such as HLA-DRB1*15:01 in European, Asian, and North American patients and HLA-DRB1*15:03 in African Americans, indicating an ethnicity-dependent pattern. For NT2, genetic associations remain poorly understood. This study aimed to assess the genetic associations of narcolepsy in a Brazilian population, considering the impact of genetic admixture. Patients were recruited from the sleep clinic at Hospital Universitário Pedro Ernesto, and their blood samples were used for DNA extraction and analyzed using two techniques: HLA typing by massive parallel sequencing and SNP (single nucleotide polymorphism) genotyping by DNA microarrays. The HLA typings were compared with controls from the Registro Brasileiro de Doadores Voluntários de Medula Óssea (REDOME) database, evaluating genetic associations, including analyses based on self-reported color/race and genetic ancestry. SNP data were used to estimate patient ancestry, enabling comparisons with self-reported data. Additionally, variants associated with narcolepsy reported in the literature were identified. The results confirmed the presence of HLA-DQB1*06:02 in all NT1 patients, with the HLA-DRB1*15:03~DQB1*06:02 haplotype being the most associated with risk, particularly in self-identified Black or mixed-race individuals. For NT2, no significant association was identified. Furthermore, five SNPs were found, with rs2834188A (IL10RB-IFNAR1) and rs1154155G (TRA) standing out due to their association with immune response, indicating risk for the development of the disease. These findings reinforce the influence of the HLA-DQB1*06:02 allele and the HLA-DRB1*15:03~DQB1*06:02 haplotype in NT1 predisposition in an admixed population. The lack of significant associations for NT2 highlights the need for further studies on its pathophysiology and reinforces the genetic differences between narcolepsy types. Investigating genetic variants contributes to understanding the immunogenetic role of narcolepsy and elucidating the mechanisms of this disorder. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação 2025-02-24T00:00:00Z http://www.bdtd.uerj.br/handle/1/24120 Título: Treinamento intervalado de alta intensidade: papel na prevenção da doença hepática gordura não alcoólica em camundongos alimentados com dieta hiperlipidica Autor: Tavares, Henrique de Souza Primeiro orientador: Souza-Mello, Vanessa Abstract: Non-alcoholic fatty liver disease (NAFLD) attracts attention from the scientific community due to its silent harmful progression and non-existence of a specific treatment. Glucolipotoxicity triggers endoplasmic reticulum (ER) stress with decreased beta-oxidation and enhanced lipogenesis, favoring NAFLD onset. Regular physical exercise could prevent NAFLD by preserving ER and mitochondrial function. This study evaluated whether high-intensity interval training (HIIT) could prevent NAFLD development in HF-fed C57BL/6, focusing on ER homeostasis and mitochondrial function. Forty male C57BL/6 mice (3 months old) made up four experimental groups: control (C) diet group, C diet + HIIT (C-HIIT) group, high-fat (HF) diet group, and HF diet + HIIT (HF-HIIT) group. HIIT sessions lasted 12 minutes and were taken thrice weekly by trained mice. Diet and exercise protocols lasted for ten weeks. HIIT protocol prevented weight gain and maintained insulin sensitivity in the HF-trained group. A chronic HF diet increased ER stress-related genes and protein expression, but HIIT achieved ER homeostasis, preserved mitochondrial ultrastructure, and maximized beta-oxidation. The increased Sirt1/Pgc1a expression implies that HIIT enhanced mitochondrial biogenesis and adequate mitochondrial dynamics. High hepatic Fndc5/irisin complied with anti-lipogenic and anti-inflammatory effects observed in the HF-HIIT group, reinforcing the anti-steatotic effects of HIIT. This study shows reliable evidence that HIIT maintained insulin sensitivity, prevented ERE, and enhanced hepatic beta-oxidation, impeding NAFLD development in this mouse model even with high energy intake from saturated fatty acids. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação 2024-02-29T00:00:00Z