Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue

Funding: This work was supported by a grant from GIFT (Grupo de Investigação Fundamental e Translational) from the Portugal Society of Diabetes and Portugal Foundation for Science and Technology (PEst UID/NEU/04539/2013 and UID/NEU/04539/2019: CNC.IBILI; PEst UIDB/04539/2020 and UIDP/04539/2020: CIBB). G.T. and D.R.S. were supported by Ph.D. Grants from the Portuguese Foundation for Science and Technology (PD/BD/127822/2016 and 2021.08160.BD respectively). J.F.S. is supported by a contract from the Portuguese Foundation for Science and Technology (CEEC IND/02428/2018).Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 (D1DR) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders.publishersversionpublishe

CREATIVITY AND ART: A POEM THAT TEACHES ABOUT SOLID HEALTH WASTE DISPOSAL

The inclusion of courses in environmental education in the curriculum of health sciences is still limited in Brazil. Then, the objective of the present study was to develop a Creative Presentation for the Solid Health Waste Disposal theme, in order to contemplate an Educational Approach in Health as a prerequisite for the Work Safety discipline, in the Technical Nursing Course. The students created a Poem that describes how solid health waste is classified, how and where each type of waste should be separated and if the waste causes any damage to the environment and/or public health. As a result, the students were stimulated with active methodologies that favor learning and allow the teaching and learning processes to surpass the walls of the school, especially when this exercise is performed by nursing students, who will be future health educators

Beneficios de las actividades gamificadoras en estudiantes con NEE

En el ámbito educativo, el uso de herramientas de gamificación es importante porque le permite personalizar el proceso de enseñanza y mejorar la interacción entre estudiantes y docentes. Además, estas herramientas brindan retroalimentación instantánea, acceso a información actualizada y el desarrollo de habilidades esenciales para el siglo XXI, como la colaboración y la resolución de problemas. Además, fomentan la inclusión al adaptar el contenido a las necesidades únicas de los estudiantes, lo que los motiva y los motiva a participar en el aprendizaje. Además, facilitan la identificación y corrección de errores de manera oportuna y brindan acceso a recursos en línea que mejoran el proceso educativo. Al preparar a los estudiantes para un mundo digitalizado y promover la igualdad de oportunidades educativas para todos, las herramientas de gamificación tienen el potencial de transformar el proceso de enseñanza-aprendizaje. Como resultado, el objetivo principal de este estudio es analizar y comprender las ventajas de las actividades gamificadoras en estudiantes con Necesidades Educativas Especiales (NEE) para mejorar su proceso de aprendizaje y promover su inclusión en la Unidad Educativa XXX. Para llevar a cabo este estudio, se emplearon técnicas descriptivas y documentales. Se realizó una encuesta no probabilística a diez docentes para evaluar su conocimiento y aplicación de herramientas de inteligencia artificial para estudiantes con NEE. Los resultados obtenidos indicaron que las herramientas de gamificación son altamente útiles y efectivas como estrategia para reforzar y facilitar el aprendizaje de estudiantes con NEE, lo que subraya la importancia de su implementación en el entorno educativo actual.The relevance of having gamification tools in the educational field lies in their ability to personalize the teaching process and improve the interaction between students and teachers. Additionally, these tools offer immediate feedback, access to up-to-date information, and development of essential 21st century skills such as collaboration and problem solving. Likewise, they promote inclusion by adapting content to the individual and specific needs of students, which fosters their motivation and commitment to learning. In addition, they allow errors to be identified and corrected in a timely manner and offer access to online resources that enrich the educational process.Gamification tools have the potential to transform the teaching-learning process by preparing students for a digitalized world and promoting equal educational opportunities for all. Therefore, the main objective of this study is to analyze and understand the benefits of gamification activities in students with Special Educational Needs (SEN) in order to improve their learning process and promote their inclusion in the XXX Educational Unit. To carry out this study, a descriptive and documentary methodology was used. Ten teachers selected in a non-probabilistic way were surveyed to measure their knowledge and application of artificial intelligence tools aimed at students with SEN. The results obtained indicated that gamification tools are highly useful and effective as a strategy to reinforce and facilitate the learning of students with SEN, which underlines the importance of their implementation in the current educational environment

Associação entre fraturas e quedas recorrentes, sintomatologia e orientação em saúde: ossos de vidro

Osteogenesis imperfecta is a rare hereditary disease characterized by a deficiency in the production of type I collagen that interferes with connective tissue, culminating in recurrent fractures with minimal trauma due to bone fragility. In most cases, the disease results from mutations in the COL1A1 and COL1A2 genes, responsible for encoding the type I collagen chain. It is a descriptive study, with a qualitative approach, of the experience report type, with activities developed during the class practice of the subject of Semiology II, in a hospital in the city of Caratinga-MG, portraying the medical care provided to a patient with osteogenesis imperfecta. Thus, the following steps were taken: data collection during anamnesis, physical examination and consultation of medical records. It refers to a male patient, 65 years old, farmer, diagnosed with the disease, hospitalized for a fracture of the right lower limb in the portion of the diaphysis of the femur, totally displaced. In short, the present study aims to contribute to the dissemination of knowledge about osteogenesis imperfecta, given the scarcity of publications and scientific studies on this disease, exploring the clinical and symptomatological history of a patient with osteogenesis imperfecta, highlighting the necessary conducts and guidelines for a good prognosis.A osteogênese imperfeita é uma doença hereditária, rara, caracterizada pela deficiência na produção de colágeno tipo I que interfere no tecido conjuntivo, culminando em fraturas recorrentes a mínimos traumas devido à fragilidade óssea. Na maioria dos casos, a doença resulta de mutações nos genes COL1A1 e COL1A2, responsáveis por codificar a cadeia de colágeno tipo I. Trata-se de um estudo descritivo, de abordagem qualitativa, do tipo relato de experiência, com atividades desenvolvidas durante a aula prática da matéria de Semiologia II, em um hospital da cidade de Caratinga-MG, retratando o atendimento médico prestado a um paciente com osteogênese imperfeita. Atendeu-se assim às etapas: coleta de dados durante anamnese, exame físico e consulta ao prontuário. Refere-se a um paciente sexo masculino, 65 anos, lavrador, com diagnóstico da doença, internado por fratura de membro inferior direito na porção da diáfise do fêmur, totalmente desviada. Em suma, o presente estudo tem como objetivo contribuir na divulgação de conhecimento sobre a osteogênese imperfeita, frente à escassez de publicações e estudos científicos perante tal enfermidade, explorando a história clínica e sintomatológica de um paciente com osteogênese imperfeita, salientando as condutas e orientações necessárias para um bom prognóstico

Associação entre fraturas e quedas recorrentes, sintomatologia e orientação em saúde: ossos de vidro

Osteogenesis imperfecta is a rare hereditary disease characterized by a deficiency in the production of type I collagen that interferes with connective tissue, culminating in recurrent fractures with minimal trauma due to bone fragility. In most cases, the disease results from mutations in the COL1A1 and COL1A2 genes, responsible for encoding the type I collagen chain. It is a descriptive study, with a qualitative approach, of the experience report type, with activities developed during the class practice of the subject of Semiology II, in a hospital in the city of Caratinga-MG, portraying the medical care provided to a patient with osteogenesis imperfecta. Thus, the following steps were taken: data collection during anamnesis, physical examination and consultation of medical records. It refers to a male patient, 65 years old, farmer, diagnosed with the disease, hospitalized for a fracture of the right lower limb in the portion of the diaphysis of the femur, totally displaced. In short, the present study aims to contribute to the dissemination of knowledge about osteogenesis imperfecta, given the scarcity of publications and scientific studies on this disease, exploring the clinical and symptomatological history of a patient with osteogenesis imperfecta, highlighting the necessary conducts and guidelines for a good prognosis.A osteogênese imperfeita é uma doença hereditária, rara, caracterizada pela deficiência na produção de colágeno tipo I que interfere no tecido conjuntivo, culminando em fraturas recorrentes a mínimos traumas devido à fragilidade óssea. Na maioria dos casos, a doença resulta de mutações nos genes COL1A1 e COL1A2, responsáveis por codificar a cadeia de colágeno tipo I. Trata-se de um estudo descritivo, de abordagem qualitativa, do tipo relato de experiência, com atividades desenvolvidas durante a aula prática da matéria de Semiologia II, em um hospital da cidade de Caratinga-MG, retratando o atendimento médico prestado a um paciente com osteogênese imperfeita. Atendeu-se assim às etapas: coleta de dados durante anamnese, exame físico e consulta ao prontuário. Refere-se a um paciente sexo masculino, 65 anos, lavrador, com diagnóstico da doença, internado por fratura de membro inferior direito na porção da diáfise do fêmur, totalmente desviada. Em suma, o presente estudo tem como objetivo contribuir na divulgação de conhecimento sobre a osteogênese imperfeita, frente à escassez de publicações e estudos científicos perante tal enfermidade, explorando a história clínica e sintomatológica de um paciente com osteogênese imperfeita, salientando as condutas e orientações necessárias para um bom prognóstico

Measuring adherence to inhaled control medication in patients with asthma: Comparison among an asthma app, patient self‐report and physician assessment

Background Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0–100). Results A total of 193 patients (72% female; median [P25–P75] age 28 [19–41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0–71]%; 1 month: 18 [0–48]%) than patient self-report (80 [60–95]) and physician assessment (82 [51–94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio

CROSSTALK INTESTINO-TECIDO ADIPOSO: EXPLORANDO OS MECANISMOS MEDIADOS PELA GRELINA NA REGULAÇÃO DA ANGIOGÉNESE DO TECIDO ADIPOSO

Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e TecnologiaIntrodução e Objetivos: A disfunção do tecido adiposo e a desregulação da secreção de hormonas intestinais constituem dois dos principais pilares da síndrome metabólica e da diabetes mellitus tipo 2. Terapêuticas que têm como base a remodelação do trato gastrointestinal resultam numa melhoria substancial da função do tecido adiposo, ao mesmo tempo que induzem a normalização do perfil de secreção das hormonas intestinais, nomeadamente da grelina, uma hormona associada à fome e à ativação de neurónios orexigénicos que expressam neuropéptido Y. Recentemente, a grelina foi proposta como um sensor de nutrientes, visto que a sua acilação depende de ácidos gordos provenientes da alimentação, o que pode sugerir um papel desta hormona no armazenamento de nutrientes no tecido adiposo. Assim, a nossa hipótese é que o sistema grelina/neuropéptido Y esteja alterado no tecido adiposo de indivíduos obesos com síndrome metabólica, e que possa ser modelado através da cirurgia metabólica. Para além disso, temos como objetivo explorar o efeito da grelina nos adipócitos e, naturalmente, no adipo-vascular coupling.Materiais e Métodos: O perfil de expressão genética do eixo grelina/neuropéptido Y no tecido adiposo visceral de indivíduos obesos com desregulação metabólica foi avaliado através de uma reação em cadeia de polimerase em tempo real. Adicionalmente, avaliámos a ação da cirurgia metabólica neste eixo em ratos Goto-Kakizaki mantidos numa dieta altamente calórica e submetidos a gastrectomia vertical em sleeve. O efeito direto da grelina acilada e não acilada em adipócitos foi investigado na linha celular 3T3-L1 e o efeito em células endoteliais foi estudado em celúlas endoteliais microvasculares humanas. Resultados: O nosso grupo mostrou que o sistema neuropéptido Y e recetores está profundamente alterado no tecido adiposo visceral de indivíduos obesos ao longo da progressão da desregulação metabólica. A expressão dos recetores Y1 e Y5 diminuiu com o desenvolvimento da diabetes tipo 2 e o recetor Y2 com o aparecimento da insulinoresistência. Mais ainda, os intermediários deste sistema estão correlacionados com vários genes envolvidos no metabolismo, plasticidade e função endócrina do tecido adiposo. Ambos os recetores Y1 e Y2 sofreram um aumento em ratos submetidos à gastrectomia vertical em sleeve, enquanto o recetor da grelina acilada se encontrou diminuído. A grelina acilada e não acilada induziram acumulação lipídica e adipogénese em adipócitos e não alteraram a viabilidade de células endoteliais microvasculares.Conclusão: O sistema neuropéptido Y e recetores correlaciona-se com fatores envolvidos na regulação do metabolismo, angiogénese e função endócrina no tecido adiposo visceral, e sofre alterações com o agravamento da desregulação metabólica, em indivíduos obesos, constituindo assim um interessante alvo terapêutico para a síndrome metabólica e diabetes tipo 2. Ambas as formas da grelina são capazes de induzir acumulação lipídica e adipogénese, corroborando a ideia desta hormona como um sensor metabólico. Por fim, o nosso trabalho mostrou que a gastrectomia vertical em sleeve é uma ferramenta que permite modelar o eixo grelina/neuropéptido Y no tecido adiposo visceral.Introduction and Objectives: Adipose tissue dysfunction and gut secretome dysregulation constitute two of the main pillars of metabolic syndrome and type 2 diabetes mellitus. Gut remodelling-based therapies for metabolic syndrome and type 2 diabetes mellitus, result in substantial improve on adipose tissue health while, inducing a normalization of gut hormones secretion, namely ghrelin’s, a hormone highly associated to hunger and orexigenic neuropeptide Y-expressing neurons activation. Recently, ghrelin has been proposed to display a role as a nutrient sensor, since its acylation is dependent on fatty acid chains derived from ingested food, which might suggest a role for ghrelin in nutrient storage in adipose tissue. Thus, we hypothesized that the adipose tissue ghrelin/neuropeptide Y system could be altered in obese subjects with metabolic syndrome and could be modulated by metabolic surgery. Furthermore, we aimed to explore the effect of ghrelin in adipocytes and, naturally, in the adipo-vascular coupling.Materials and Methods: Genetic expression profiling of the ghrelin/neuropeptide Y axis in the visceral adipose tissue of obese subjects with metabolic dysregulation was performed by a high-throughput real-time polymerase chain reaction. Additionally, we assessed the effect of metabolic surgery in ghrelin/neuropeptide Y axis in Goto-Kakizaki rats fed a high caloric diet and submitted to vertical sleeve gastrectomy. The direct effects of ghrelin and des-acyl ghrelin in adipocytes were investigated in a 3T3-L1 fibroblasts cell line and the effects in endothelial cells were studied in human microvascular endothelial cells. Results: Our group showed that the neuropeptide Y/Y receptors system is deeply altered in visceral adipose tissue, with the progression of metabolic dysregulation in obese individuals. Y1 and Y5 receptors were downregulated with type 2 diabetes development and the Y2 receptor with insulin resistance onset. Furthermore, intermediates of this system are correlated with several genes involved in adipose tissue metabolism, plasticity and endocrine behaviour. Both Y1 and Y2 receptors were increased in the peri epididymal adipose tissue of rats submitted to vertical sleeve gastrectomy, while acylated ghrelin receptor levels were decreased. Acylated and non-acyl ghrelin induced lipid accumulation and adipogenesis in adipocytes and did not alter the viability of human microvascular endothelial cells.Conclusion: The neuropeptide Y/Y receptors system correlates with factors involved in the regulation of metabolism, angiogenesis and adipokine secretion regulation in visceral adipose tissue and is deeply altered with the aggravation of metabolic dysregulation, in obese individuals, thus constituting an interesting therapeutical target for metabolic syndrome and type 2 diabetes. Ghrelin (both forms) is able to directly induce lipid accumulation and adipogenesis, supporting a role as a nutrient sensor. Lastly, our work showed that vertical sleeve gastrectomy is a tool to remodel the ghrelin/neuropeptide Y axis in visceral adipose tissue

The Bidirectional Relationship of NPY and Mitochondria in Energy Balance Regulation

Energy balance is regulated by several hormones and peptides, and neuropeptide Y is one of the most crucial in feeding and energy expenditure control. NPY is regulated by a series of peripheral nervous and humoral signals that are responsive to nutrient sensing, but its role in the energy balance is also intricately related to the energetic status, namely mitochondrial function. During fasting, mitochondrial dynamics and activity are activated in orexigenic neurons, increasing the levels of neuropeptide Y. By acting on the sympathetic nervous system, neuropeptide Y modulates thermogenesis and lipolysis, while in the peripheral sites, it triggers adipogenesis and lipogenesis instead. Moreover, both central and peripheral neuropeptide Y reduces mitochondrial activity by decreasing oxidative phosphorylation proteins and other mediators important to the uptake of fatty acids into the mitochondrial matrix, inhibiting lipid oxidation and energy expenditure. Dysregulation of the neuropeptide Y system, as occurs in metabolic diseases like obesity, may lead to mitochondrial dysfunction and, consequently, to oxidative stress and to the white adipose tissue inflammatory environment, contributing to the development of a metabolically unhealthy profile. This review focuses on the interconnection between mitochondrial function and dynamics with central and peripheral neuropeptide Y actions and discusses possible therapeutical modulations of the neuropeptide Y system as an anti-obesity tool

Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue

Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 (D1DR) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders