The prevalence of obesity and, consequently, diabetes has been increasing exponentially in recent decades, on a global scale, and this trend is expected to continue in the coming years. Therefore, there is an urgent need for new therapies to help us change this trajectory. Tirzepatide, the first of a new pharmacological class named co-agonists or dual agonists of the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic peptide (GIP), has demonstrated in clinical trials published in the last two years, to significantly reduce blood glucose, improve insulin resistance and reduce body weight, with additional benefits on hypertension and lipid profile. Additional data on its impact on cardiovascular endpoints are eagerly awaited. In this article it is presented a review of this new drug and the new perspectives that its appearance will open, in the future of the treatment of diabetes and obesity

Abstract Background: We aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) in clinical practice. Research design and methods: A total of 340 patients were included. Data on age, gender, antidiabetic medications, and bioanalytical parameters were collected at baseline and one year later. Were analyzed estimated glomerular filtration rate (eGFR), blood sodium and potassium levels, blood pressure, weight, cardiovascular risk, and glycated hemoglobin (HbA1c). Results: Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline (p = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i (p = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint (p < 0.0001), with a higher percentage of patients achieving ≥ 5% weight loss compared to the non-GLP1RA group (33.6% vs. 19.8%). Both SGLT2i and GLP1RA treatments significantly reduced cardiovascular risk scores (p = 0.004 and p = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint (p = 0.010 and p = 0.002, respectively). Conclusions: Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM.

Obesity has grown to pandemic proportions. It affects an increasing number of children, adolescents and young adults exposed to the silent comorbidities of this disorder for a longer period. Infertility has arisen as one important comorbidity associated with the energy dysfunction promoted by obesity. Spermatogenesis is a highly regulated process that is determined by specific energetic requirements. The reproductive potential of males relies on hormonal-dependent and -independent stimuli that control sperm quality. There are conflicting data concerning the impact of male overweight and obesity on sperm quality, as well as on the possible paternal-induced epigenetic trait inheritance of obesity. In addition, it remains a matter of debate whether massive weight loss induced by lifestyle interventions, drugs or bariatric surgery may or may not benefit obese men seeking fatherhood. Herein, we propose to discuss how energy balance may modulate hormonal signalling and sperm quality in overweight and obese men. We also discuss some molecular mechanisms that mediate obesity-related dysfunction in male reproductive system and how paternal obesity may lead to trait inheritance. Finally, we will discuss how lifestyle modifications and sustained weight loss, particularly the loss achieved by bariatric surgery, may revert some of the deleterious effects of obesity in men and their offspring.

Prostate cancer (PCa) is a hormone-dependent cancer whose development and progression are strongly influenced by the tumour microenvironment and exogenous factors, such as environmental influences. The periprostatic adipose tissue (PPAT), by its anatomical proximity and functional crosstalk with prostate cells, emerged as a key driver of tumour growth, particularly in obesity, with the secretome of “obese” PPAT being associated with enhanced tumour aggressiveness. On the other hand, epidemiological and experimental studies have implicated endocrine-disrupting chemicals (EDCs) as environmental risk factors for PCa. Given the hormone dependency of PCa, it is predictable that it is a cancer highly susceptible to the influence of environmental exposures, namely EDCs and specifically those with obesogenic properties (i.e. obesogens), which are capable of disrupting both endocrine and metabolic pathways. Notably, based on their mechanisms of action and the cellular and molecular alterations they induce, obesogens may promote tumorigenesis either directly by acting on prostate cells or indirectly by inducing adipose tissue dysfunction. However, the extent to which obesogenic compounds drive these alterations and the consequent impact on prostate tumorigenesis remain largely unknown. Moreover, despite the well-established effects of obesogens on adipose tissue, no study has characterised their actions on PPAT. Addressing these gaps is critical to understanding how environmental factors intersect with adipose tissue biology, influencing interorgan communication between the prostate and adipose tissue and PCa development. Based on this scientific rationale, this doctoral thesis hypothesises that obesogen-induced PPAT dysfunction represents a driving force in the initiation and progression of PCa. Tributyltin (TBT) is a well-characterised obesogenic EDC and a potent regulator of adipogenesis, widely used in experimental settings to investigate the effects of obesogens. Therefore, using the obesogen model TBT this thesis aimed to: (i) characterise the morphological and secretory alterations of PPAT following TBT exposure; (ii) assess the impact of TBT-induced PPAT dysregulation on prostate cell fate, metabolism, oxidative and inflammatory status, and response to chemotherapeutic drugs; and (iii) identify the molecular targets and signalling pathways mediating the crosstalk between dysregulated PPAT and prostate cells. First, it was demonstrated that in vivo exposure to TBT (50 μg/kg) besides increasing rat body weight, enhanced PPAT somatic index and altered its functional phenotype. TBT treatment promoted a shift in rat prostate cells toward a glycolytic and lipogenic metabolic profile and stimulated oncogenic signalling pathways, including increased phosphorylated/total protein kinase B (pAKT/AKT) ratio and androgen receptor expression. Moreover, macrophage infiltration and a shift in macrophage polarisation towards a pro-inflammatory phenotype were observed both in the prostate and PPAT of TBT-exposed animals, suggesting that TBT can perturb the local prostate-PPAT immune status, contributing to an environment permissive to prostate carcinogenesis. These findings confirmed the effects of TBT on prostate cells, supporting the hypothesis and the investigation into the contribution of PPAT-mediated effects in altering prostate cell behaviour. Culture of the PPAT from rats exposed to TBT clearly demonstrated that TBT induced a dysregulation of the PPAT secretome. TBT-treated PPAT (TBT-PPAT) displayed increased leptin/adiponectin ratio and C-C motif chemokine ligand 7 (CCL7) levels. This adipokine/chemokine profile induced by TBT mimics that observed in obesity and is concurrent with a metabolic reprogramming associated with enhanced glucose, free fatty acids, and lipid peroxidation. Importantly, ex vivo exposure of rat PPAT to TBT (100 nM) recapitulated the findings obtained in vivo concerning the features of its secretome, which are capable of having an impact on prostate cell fate. The results obtained in the subsequent preclinical approaches using co-cultures and conditioned media (CM) assays confirmed the ability of TBT-PPAT enhance the viability, proliferation and migration, as well as apoptosis resistance, in all the studied prostate cell line models, namely non-neoplastic prostate epithelial cells (PNT1A), and androgen-sensitive (22Rv1) and androgen-insensitive (DU145 and PC3) PCa cells. Notably, the TBT-PPAT secretome increased the expression of CCL7 receptor, the C-C motif receptor 3 (CCR3), in prostate cells, which, together with the enhanced CCL7 secretion observed in our experimental setting, raised curiosity about the role of the CCL7-CCR3 axis underlying the pro-tumorigenic effects of TBT-PPAT. The use of a CCR3 antagonist significantly reduced TBT-PPAT induced migration across all cell lines, allowing to implicate the CCL7 and CCR3 in the observed responses of prostate cells. Other molecular targets beyond the CCL7-CCR3 axis were also highlighted. It is the case of tribbles homolog 1 (TRIB1), a pseudokinase involved in tumorigenesis and lipid homeostasis that was overexpressed across all studied cell models exposed to TBT-PPAT-CM. Cell fate alterations observed upon TBT treatment were accompanied by metabolic changes with distinct outcomes in non-neoplastic and neoplastic cell lines: in PNT1A, enhanced fatty acid β-oxidation and synthesis indicate a plausible shift toward a cancer-like metabolic profile; in 22Rv1, the unaltered metabolic and oxidative status suggests the activation of alternative signalling pathways sustaining TBT-PPAT effects; in DU145 and PC3, the distinct metabolic responses observed underscore the differential responsiveness of androgen-insensitive PCa cell subtypes to adipose-derived cues. The investigation in the present thesis was extended to a clinically relevant setting. Human PPAT obtained from patients submitted to radical prostatectomy or prostatic adenomectomy (Millin’s procedure) was treated ex vivo with TBT (100 nM) to confirm if the human tissues resemble the pro-tumorigenic cues identified in controlled experimental models. This approach demonstrated that human PPAT is a target of obesogenic dysregulation and showed that the secretome of obesogen-dysregulated PPAT can significantly enhance the viability of prostate cells. Moreover, the presence of human TBT-PPAT reduced the sensitivity of PCa cells to docetaxel and cabazitaxel, suggesting that obesogenic dysregulation contributes to PCa resistance to taxane-based chemotherapy. Overall, the scientific evidence gathered in this thesis identifies PPAT as a key target of obesogenic EDCs, which disrupt PPAT function and its crosstalk with prostate cells, thereby contributing to the initiation and progression of PCa. These findings open new avenues for developing interventions aimed at modulating PPAT activity to counteract its tumour-promoting effects and emphasise obesity as a critical modulator of PCa aggressiveness.

O Estágio Pedagógico, inserido no 2º ano do Mestrado em Ensino de Educação Física (EF) nos Ensinos Básico e Secundário da UBI, tem como objetivo que os alunos experienciem de uma forma prática, o contexto e realidade escolar, assim como todas as funções que competem a um Professor. Apresentamos ao longo do Relatório uma descrição de todo o trabalho desenvolvido, bem como uma reflexão nas diversas áreas de intervenção, ao longo do ano letivo 2016/2017 no Estágio realizado no Centro de Estudo de Fátima. O Relatório encontra-se dividido em dois grandes capítulos: no primeiro abordamos algumas tarefas referentes ao planeamento, à intervenção e à avaliação. O contacto com métodos de trabalho diferentes, as experiências e a relação social entre alunos da turma, professores, orientador, funcionários, a descoberta de lacunas na nossa formação profissional, a ligação entre a teoria e a prática, as dificuldades sentidas e a sua forma de resolução, assim como um conjunto de conhecimentos e competências pedagógicas adquiridas, tornaram este este processo de formação mais motivador e uma mais valia fundamentais para o processo ensino-aprendizagem e desempenho futuro nas tarefas referentes à docência. O segundo capítulo é dedicado ao trabalho de investigação. A obesidade infantil tem revelado níveis alarmantes, sendo que os índices de prática desportiva e de atividade física em crianças tem baixado nos últimos anos. Sabendo a importância que a atividade física regular tem também neste âmbito tornou-se essencial uma intervenção junto de crianças de modo a torná-las mais ativas e promovendo um estilo de vida saudável. Foi criado e implementado, em conjunto com o Núcleo de Educação para a Saúde da Escola, um programa de intervenção e controlo de obesidade para alunos do 2º ciclo, com o intuito de aumentar os níveis e hábitos de atividade física, bem como meio de controlo regular e monitorização da sua alimentação e níveis de composição corporal. Os resultados obtidos, permitem concluir que a implementação de um programa multidisciplinar com o acompanhamento nutricional, monitorização de índices corporais bem como a prescrição de sessões práticas aliedas aos gostos e motivações dos alunos, poderão ter resultados bastante satisfatórios nos vários domínios.

Introdução: A pré-eclampsia é uma doença hipertensiva da gravidez que representa uma das principais causas de morbimortalidade materna e fetal. Está associada a proteinúria e, por vezes, edema patológico, que se desenvolve após as 20 semanas de gestação. Um dos fatores de risco para o desenvolvimento de pré-eclampsia é a obesidade materna, uma condição caracterizada pela disfunção do tecido adiposo e, consequentemente, alterações no padrão de secreção hormonal. Apesar da fisiopatologia da pré-eclampsia não estar totalmente esclarecida, a maioria dos autores defende que a existência de uma falha na transformação das artérias espirais uterinas, devido a uma anomalia na invasão do trofoblasto durante o processo de placentação, é a explicação para o desenvolvimento desta patologia. Assim, como a adiponectina é influenciada pelas variações percentuais do tecido adiposo corporal e tem a capacidade de atuar na placenta, desempenhando um papel significativo na regulação dos processos associados à placentação, é colocada a hipótese de existir relação entre a alteração do padrão de secreção hormonal da adiponectina e o desenvolvimento de préeclampsia. Objetivo: Analisar o papel da adiponectina como biomarcador da pré-eclampsia ou ponderar a necessidade de adicionar outros biomarcadores, além da adiponectina, para o desenvolvimento de testes de rastreio e implementação de estratégias de prevenção e intervenção precoces. Métodos: Esta revisão sistemática foi realizada de acordo com as linhas orientadoras do Fluxograma PRISMA 2020, cujo protocolo foi submetido na base de registo de protocolos e revisões sistemáticas PROSPERO (ID CRD42024542403). Para a sua realização foram consultadas as seguintes bases de dados: PubMed e Scopus. A pesquisa decorreu entre março e 30 de julho de 2023. Foram pesquisados artigos originais utilizando as seguintes palavras-chave MeSh: “Preeclampsia” AND “Adiponectin” na base de dados PubMed e “Preeclampsia” [Abstract] AND “Adiponectin” [Abstract] na base de dados Scopus. Resultados: Após a aplicação dos critérios de exclusão e inclusão, foram selecionados 30 estudos para a realização desta revisão sistemática. Entre eles, estão presentes estudos de caso-controlo, de coorte prospetiva e retrospetiva, estudos transversais e de randomização mendeliana bidirecional. A amostra de participantes variou entre 52 e 141068, englobando populações de 14 países diferentes. As características dos diferentes estudos foram bastante variáveis e existiu grande heterogeneidade nos resultados obtidos pelos diversos estudos. Há estudos que revelaram um aumento da adiponectina na pré-eclampsia, outros uma diminuição e alguns não detetaram qualquer alteração nos níveis da glicoproteína. Foram ainda identificados estudos onde não foi possível determinar os níveis de adiponectina, impossibilitando a realização de qualquer tipo de associação. Discussão: Através da realização e interpretação de uma tabela, onde é identificado o nível de evidência dos diferentes estudos incluídos, é percetível a predominância dos níveis de evidência moderado e baixo, sendo a evidência superior quando observamos uma diminuição dos níveis de adiponectina na pré-eclampsia. Inúmeros fatores podem explicar a divergência de resultados obtida, tais como o momento de recolha das amostras para análise, o tipo de amostras recolhidas, o tamanho da amostra, o índice de massa corporal considerado, a etnia, entre outros. Conclusão: Perante os resultados contraditórios encontrados é fulcral promover o desenvolvimento de estudos e investigação científica nesta área. Deve ainda ser proposta a possibilidade de associar a adiponectina a outros biomarcadores. A identificação de biomarcadores permitirá o desenvolvimento de métodos de rastreio e diagnóstico, proporcionando a deteção precoce e a implementação de estratégias preventivas e terapêuticas específicas, limitando o aparecimento de complicações e resultados adversos tanto para a mãe como para o feto.

Objective: The study aims to identify and analyze the influence of body composition and basal metabolic rate over the behavior of temporal parameters of ground reactive forces during the gait of postmenopausal. Methods: The experimental study was carry out with 52 women (±59.8 years). The fat mass, abdominal visceral adiposity, skeletal muscle mass, fat-free mass and basal metabolic rate have evaluated by octopolar bioimpedance. The data for the ground reactive forces were collect through the force platform. Results: In relative terms, the fat mass showed influence the final phase of support, causing a decrease in this parameter. Abdominal visceral adiposity also exerted inverse influence on the vertical loading (r = -0.31) and unloading (r = -0.35) rate. The skeletal muscle mass (r = -0.45, r = -0.46; p<0.01) and basal metabolic rate (r = -0.44, r = -0.46; p<0.01) influenced the vertical loading rate and the relationship between the vertical rates significantly. Conclusion: The study suggests that the increase on fat mass and abdominal visceral adiposity, influence the support time and the vertical rates. With a more robust skeletal muscle system the postmenopausal women exhibit the phases of the gait cycle less accentuated, signaling less stress on the joints.

Type 2 Diabetes Mellitus (T2DM) is a highly prevalent chronic disease associated with substantial morbidity and mortality, largely driven by cardiovascular (CV) complications, chronic kidney disease (CKD), and obesity. The global burden of T2DM continues to rise, fueled by aging populations, urbanization, and lifestyle-related risk factors. In this context, newer therapeutic classes such as sodium-glucose cotransporter2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) have transformed the management of T2DM by providing benefits that extend far beyond glycemic control. Robust evidence demonstrates that these agents reduce the risk of major adverse cardiovascular events (MACE), slow CKD progression, promote weight loss, and improve metabolic parameters. As a result, both drug classes have been increasingly repositioned and approved for new clinical indications, broadening their use to diverse and often complex patient populations. Despite substantial evidence from randomized controlled trials, real-world data on the safety and effectiveness of SGLT2i and GLP1RA remain essential, particularly in older individuals, polymedicated patients, and those with multiple comorbidities—groups often underrepresented in clinical trials. Post-marketing safety signals, including genitourinary infections with SGLT2i and gastrointestinal adverse effects with GLP1RA, underscore the need for continued pharmacovigilance. Understanding how these medicines perform in routine care settings is critical to optimizing therapeutic strategies and supporting clinical decision-making. This doctoral thesis aimed to evaluate the safety and effectiveness profiles of SGLT2i and GLP1RA using real-world data from hospital settings and pharmacovigilance reports. Retrospective observational studies were conducted across emergency departments, inpatient hospitalizations, and outpatient consultations, complemented by an analysis of adverse drug reaction (ADR) reports from the EudraVigilance (EV) database. Key findings highlight the effectiveness of SGLT2i in improving renal function, reducing systolic blood pressure, and lowering hospitalization rates for heart failure (HF). GLP1RA were particularly effective in achieving significant weight loss and reducing CV risk scores. Both drug classes demonstrated substantial reductions in glycated hemoglobin (HbA1c), consistent with clinical trial data. Safety analyses revealed low incidences of acute kidney injury (AKI) and major CV events, with gastrointestinal side effects being the most frequently reported ADRs for GLP1RA. These results underscore the critical role of SGLT2i and GLP1RA in comprehensive T2DM management, particularly for high-risk populations with multiple comorbidities. The findings also emphasize the need for ongoing pharmacovigilance and tailored therapeutic strategies to optimize patient outcomes. Future research should focus on mitigating adverse effects and validating these findings across diverse populations and healthcare settings.

Introdução: Ao longo das últimas décadas houve um acréscimo das crianças e adolescentes com excesso de peso ou obesidade, o que tem trazido preocupações a nível mundial. A prevalência tem aumentado e tem provocado comorbilidades importantes, nomeadamente físicas, psicológicas, económicas e sociais, tanto a curto como a longo prazo. A obesidade é uma doença crónica, mas quando detetada atempadamente consegue ser tratada. A abordagem é limitada e multimodal enfatizando em primeira linha modificações de estilo de vida, contudo têm produzido efeitos pouco duradouros. Objetivos: O presente trabalho tem como objetivo analisar o tratamento da obesidade em crianças e adolescentes (idade entre os 6 e os 18 anos) com o liraglutido, e assim verificar se existe uma utilização segura e eficiente para estas faixas etárias deste fármaco, bem como os possíveis mecanismos pelos quais ele atua. Métodos: Para a elaboração desta monografia, procedeu-se à pesquisa de artigos na plataforma PubMed, Scopus e Web of Science, com as seguintes palavras-chave; “liraglutide”, “child”, “adolescent”, “obesity”, “Glucagon-Like Peptide 1”, e os seguintes operadores booleanos, “AND” e “OR”. Resultados: Foram analisados 8 artigos que abordavam o tratamento da obesidade usando o liraglutido nestas faixas etárias. Na generalidade, foram identificados resultados que traduzem redução do peso e IMC médio, resolução de complicações associadas, melhoria de sintomas relacionados com ansiedade e depressão, melhoria do perfil metabólico e cardiovascular. Discussão e Conclusões: Este trabalho permitiu observar que este fármaco, o liraglutido, é dentro dos fármacos desta classe o mais prescrito. Contudo, este trabalho apresentou várias limitações, nomeadamente o número reduzido de estudos, o tempo reduzido de administração deste fármaco ou a amostra pequena. A tolerância do paciente a este fármaco também foi determinante para a duração do tratamento, tendo em conta, maioritariamente efeitos gastrointestinais, causados. De maneira concisa, os estudos analisados oferecem resultados promissores, eficazes e seguros, onde o liraglutido apresenta um papel importante na redução de IMC e do peso corporal associado a um estilo de vida saudável, contudo, ainda há muitos parâmetros e consequências por compreender, sendo necessária mais investigação sobre o tema antes de uma conclusão. Assim sendo, atualmente ainda é difícil determinar a eficácia a longo prazo da injeção de liraglutido.

Objective: This study aimed to investigate the foot contact time differences between obese and nonobese subjects during walking when crossing obstacles. Methods: Ninety-eight postmenopausal women were assigned to four groups, and their plantar pressure temporal data were collected using a two-step protocol during walking when crossing an obstacle set at 30% height of lower limb length of each subject. The initial, final, and duration of contact of 10 foot areas were measured. Results: Leading limb: (1) the heel groups initiated foot contact using the heel, and the non-heel groups initiated contact using the metatarsals; (2) heel obese subjects showed an earlier initial contact and a longer contact duration of metatarsals 2–3; (3) non-heel obese subjects showed an earlier midfoot initial contact. Regarding the trailing limb: (4) heel obese subjects showed an earlier midfoot initial contact and a longer contact duration of metatarsal 5; (5) non-heel obese subjects showed an earlier initial contact and a longer contact duration of metatarsals 4–5. Conclusions: (1) The non-heel groups’ foot rollover pattern may result from an attempt of rapidly restoring stability; (2) the heel obese subjects seem to regulate their plantar foot muscles to overcome their overweight; (3) the overweight of the non-heel obese subjects leads to a quicker backward foot roll-over from the metatarsals to the heel; (4) the overweight of the heel obese subjects can distort their footprints and/or their higher inertia may precipitate an anticipation of the midfoot contact, which can also explain the result observed for 5.