http://www.bdtd.uerj.br/handle/1/3535 Mon, 11 May 2026 18:15:52 GMT 2026-05-11T18:15:52Z 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 Tue, 01 Jul 2025 00:00:00 GMT http://www.bdtd.uerj.br/handle/1/24518 2025-07-01T00:00:00Z http://www.bdtd.uerj.br/handle/1/23845 Título: Agonista duo PPAR alfa/gama: plasticidade e longevidade das ilhotas pancreáticas num modelo experimental de obesidade Autor: Fernandes-da-Silva, Aline Primeiro orientador: Mello, Vanessa de Souza Abstract: The pancreas is an essential organ for metabolic regulation but is also highly vulnerable to lipotoxicity, a condition associated with excess fat and common in obesity states. This lipotoxicity compromises the structure and function of pancreatic islets, impacting insulin secretion and worsening glycemic imbalance. Therapeutic strategies that preserve beta-cell functionality and restore metabolic homeostasis are essential to prevent or manage type 2 diabetes mellitus (T2DM). In this context, activation of peroxisome proliferator-activated receptors (PPAR)a/g, known for their role in regulating lipid metabolism and inflammation, has emerged as a promising approach. This study investigated the effects of isolated and combined activation of PPARa and PPARg receptors on pancreatic islet remodeling, beta-cell proliferation, identity, and maintenance in a diet-induced obesity experimental model. Mice were fed a high-fat diet (HF) for ten weeks, followed by four weeks of treatment with PPARa, PPARg, or dual PPARa/g receptor agonists. The HF-fed animals exhibited glucose intolerance, a pro-inflammatory adipokine profile, increased beta- and alpha-cell mass, and gene expression indicative of beta-cell dedifferentiation and impaired proliferation. The results showed that all PPAR agonist treatments alleviated glucose intolerance, reduced body weight, and promoted an anti-inflammatory profile. However, the group treated with the combined PPARa/g agonist exhibited the greatest efficacy in restoring islet cytoarchitecture and positively regulating beta-cell identity and maintenance genes, such as Pdx1, Mafa, and Nkx6.1. These findings suggest that combined PPARa/g activation can interrupt the spectrum of metabolic complications associated with obesity, preserving beta-cell functionality and offering therapeutic potential for T2DM treatment. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese Tue, 18 Feb 2025 00:00:00 GMT http://www.bdtd.uerj.br/handle/1/23845 2025-02-18T00:00:00Z http://www.bdtd.uerj.br/handle/1/23612 Título: Cotadutida (agonista duplo GLP-1/glucagon) afeta o pâncreas, tecido adiposo marrom e hipotálamo de camundongos obesos Autor: Spezani, Renata Primeiro orientador: Mandarim-de-Lacerda, Carlos Alberto Abstract: Obesity and Type 2 Diabetes Mellitus (T2DM): A Multifaceted Impact. Obesity combined with T2DM induces profound alterations in alpha- and beta-cells, brown adipose tissue (BAT), and hypothalamic neuropeptides. Beta cells, as key regulators of insulin production, remain a primary target for cell replacement and regenerative therapies aimed at treating T2DM. Current strategies focus on enhancing beta-cell proliferation and promoting functional maturity. Meanwhile, an emerging therapeutic avenue involves reprogramming various cell types into insulin-producing cells. Among these, alpha cells stand out as promising candidates due to their phenotypic similarity to beta cells and their genomic accessibility for transdifferentiation. Cotadutide: A Novel Dual GLP-1/Glucagon Receptor Agonist. Cotadutide, a novel dual GLP-1/glucagon receptor agonist, holds potential for improving islet cell architecture and function, remodeling interscapular BAT, enhancing thermogenesis, and modulating hypothalamic neuropeptides. This study explored the effects of cotadutide in obese mice. Twelve-week-old male C57BL/6 mice were fed either a control diet (C, 10% kJ fat) or a high-fat diet (HF, 50% kJ fat) for ten weeks. Subsequently, the animals were divided into four groups and treated daily for 30 days with subcutaneous injections of cotadutide (30 nmol/kg) or vehicle: C, CC (control + cotadutide), HF, and HFC (high fat + cotadutide). Key Findings and Effects of Cotadutide. Cotadutide administration in the HFC group resulted in significant weight loss and improved insulin sensitivity. These benefits were evidenced by increased expression of insulin receptor substrate 1 and solute carrier family 2 in isolated pancreatic islets. Additionally, cotadutide enhanced transcription factors associated with islet cell transdifferentiation and alleviated markers of endoplasmic reticulum (ER) stress. In BAT, cotadutide reversed adipocyte hypertrophy, structural disarray, and lipid accumulation observed in the HF group. Furthermore, cotadutide promoted thermogenesis, increased body temperature, enhanced angiogenesis and lipolysis, and stimulated mitochondrial biogenesis. In the hypothalamus, cotadutide treatment in the HFC group improved the expression of genes linked to energy balance and associated signaling pathways, indicating modulation of the gut-brain axis. Conclusions and Implications. In conclusion, this study demonstrates that cotadutide exerts profound benefits in obese mice, including weight reduction, enhanced glycemic control, and improved insulin sensitivity. Cotadutide also ameliorated adverse remodeling of pancreatic islets by improving markers of transdifferentiation, proliferation, apoptosis, and ER stress. Additionally, its thermogenic effects on interscapular BAT and its role in energy balance modulation through the gut-brain axis provide new insights into its mechanisms of action. These findings highlight the potential translational benefits of cotadutide for addressing obesity and T2DM. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese Wed, 19 Feb 2025 00:00:00 GMT http://www.bdtd.uerj.br/handle/1/23612 2025-02-19T00:00:00Z http://www.bdtd.uerj.br/handle/1/23303 Título: Metabolismo e fígado em camundongos alimentados cronicamente com frutose: papel da vitamina D, deficiência e suplementação Autor: Ceciliano, Thais Christine Maia Primeiro orientador: Mandarim-de-Lacerda, Carlos Alberto Abstract: Fructose added to soft drinks and processed foods, as well as the frequent detection of vitamin D deficiency in the body, are two insults increasingly considered to cause target organ damage. We studied the liver after a chronic high-fructose diet deficient and supplemented with vitamin D. Sixty adult C57Bl/6 male mice were allocated into six groups (n=10) for ten weeks, according to the experimental diet: control (C), vitamin D deficient control (CDD), vitamin D supplemented control (CDS), fructose (F), vitamin D deficient fructose (FDD) and vitamin D supplemented fructose (FDS). Gene expressions of the vitamin D receptor (Vdr) and Cyp27b1 and plasma level of 25-hydroxyvitamin D ensured that diets caused vitamin D deficiency or supplementation. Body mass did not change, but blood pressure (BP) increased in CDD, F and FDD, while BP was controlled in FDS. Insulin, glucose tolerance, and insulin resistance were observed in both vitamin D deficiency and fructose groups but improved with vitamin D supplementation. Liver steatosis and fibrosis were observed in CDD, F, and FDD groups. Furthermore, F and FDD showed activation of hepatic stellate cells. Gene expressions of lipogenesis and inflammation increased in the CDD, F and FDD groups, but decreased with vitamin D supplementation. In conclusion, we demonstrated the adverse effects of vitamin D deficiency on metabolism, hepatic steatosis and, combined with fructose intake, hepatic interstitial fibrosis with hepatic stellate cell activation, and alteration of lipogenesis, beta-oxidation and hepatic inflammation. All these data improved when vitamin D was supplemented in animals. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese Mon, 04 Nov 2019 00:00:00 GMT http://www.bdtd.uerj.br/handle/1/23303 2019-11-04T00:00:00Z