Obesity is a major concern for global healthcare systems. Systemic low-grade inflammation in obesity is a major risk factor for insulin resistance. Leptin is an adipokine secreted by the adipose ...tissue that functions by controlling food intake, leading to satiety. Leptin levels are increased in obesity. Here, we show that leptin enhances the effects of LPS in macrophages, intensifying the production of cytokines, glycolytic rates and morphological and functional changes in the mitochondria through an mTORC2-dependent, mTORC1-independent mechanism. Leptin also boosts the effects of IL-4 in macrophages, leading to increased oxygen consumption, expression of macrophage markers associated with a tissue repair phenotype, and wound healing. In vivo, hyperleptinemia caused by diet-induced obesity increases the inflammatory response by macrophages. Deletion of leptin receptor and subsequently of leptin signaling in myeloid cells (ObR-/-) is sufficient to improve insulin resistance in obese mice and decrease systemic inflammation. Our results indicate that leptin acts as a systemic nutritional checkpoint to regulate macrophage fitness and contributes to obesity-induced inflammation and insulin resistance. Thus, specific interventions aimed at downstream modulators of leptin signaling may represent new therapeutic targets to treat obesity-induced systemic inflammation.
Invariant natural killer T (iNKT) cells are a distinct population of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. iNKT cells are found throughout the body, and ...little is known about their tissue-specific metabolic regulation. Here, we show that splenic and hepatic iNKT cells are metabolically comparable and rely on glycolytic metabolism to support their activation. Deletion of the pyruvate kinase M2 (Pkm2) gene in splenic and hepatic iNKT cells impairs their response to specific stimulation and their ability to mitigate acute liver injury. In contrast, adipose tissue (AT) iNKT cells exhibit a distinctive immunometabolic profile, with AMP-activated protein kinase (AMPK) being necessary for their function. AMPK deficiency impairs AT-iNKT physiology, blocking their capacity to maintain AT homeostasis and their ability to regulate AT inflammation during obesity. Our work deepens our understanding on the tissue-specific immunometabolic regulation of iNKT cells, which directly impacts the course of liver injury and obesity-induced inflammation.
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•Tissue-resident iNKT cells have unique transcriptional and metabolic signatures•PKM2 is necessary to sustain splenic and hepatic iNKT cell function•PKM2 expression in iNKT cells is necessary to mitigate acute liver injury•AMPK expression in AT-iNKT cells is necessary to improve obesity-induced AT inflammation
iNKT cells are unique among lymphocytes and are particularly unusual regarding their metabolism in different tissues. Here, Aguiar et al. show that iNKT cells in the spleen and liver rely on PKM2-driven glycolytic metabolism, while adipose tissue iNKT cells require AMPK activity and fatty acid metabolism for their function.
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular ...mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
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•Elevated glucose levels regulate viral replication and cytokine production in monocytes•Glycolysis sustains CoV-2-induced monocyte response and viral replication•mtROS/HIF-1α is necessary for CoV-2 replication and monocyte cytokine production•Monocyte-derived cytokines drive T cell dysfunction and epithelial cell death
Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with ...comorbidities associated with severe COVID-19 display higher levels of
ACE2
in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of
ACE2
. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of
ACE2
in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased
ACE2
expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.
Os recursos hídricos estão disponíveis de diversas maneiras e locais no planeta terra, sendo uma delas subterrâneas. Estas águas recebem o nome de lençol freático e estão localizadas em meio as ...rochas a baixo do nível da superfície, que podem ser classificadas em aquíferos fraturados, porosos ou cársticos. No Brasil, a captação deste recurso hídrico é feita, dentre outras maneiras, por meio de poços de água subterrâneas, que são registrados no Sistema de Informações de Águas Subterrâneas (SIAGAS). Nesse contexto, a plataforma online foi utilizada para o levantamento de todos os pontos de captação para a região do Triângulo Mineiro, salvas as exceções daqueles poços que foram perfurados e são utilizados de modo clandestino (sem registro no aparato da regulação estatal). Buscando a caracterização dos aspectos construtivos e hidrodinâmicos da região, foram realizadas análises e discussões acerca da distribuição de tais parâmetros pelo território mineiro, resultando inclusive, em estimativas de potência e energia totais para toda região, média de custos para implantação de um poço e suas emissões de dióxido de carbono. O estudo mostra que o emprego de bombas a diesel para os poços estudados, além de poluírem 37% mais o ar atmosférico, possuem um custo anual aproximadamente 141% maior em relação as bombas elétricas.
One of the most stressful human interactions is conflict. In some cases, it can bring high losses even to parties that are not involved in the conflict. A possible scenario for resolving the conflict ...can be found using a Graph Model for Conflict Resolution (GMCR) which is a tool used to analyze conflicts and present scenarios that can be seen as possible solutions to the conflict. Considering several stability criteria, in this work, we present a case study: the historical background, the modeling using the GMCR and the stable states according to the presented criteria of a conflict that occurred in Brazil, where truck drivers went on strike and generated damages to the population such as a supply crisis (of food, medicines, fuel, among other products) and financial losses to the government (delay in the flow of goods, crowding of ports, among others), mainly in cities far from large urban centers and in centers for the flow of goods by road.
Introdução: A detecção precoce de doenças cardiovasculares é fundamental para o diagnóstico e tratamento eficazes. A utilização de imagens de ultrassonografia Doppler tem sido estudada como uma ...ferramenta promissora nesse contexto. Objetivo: objetiva-se através deste, apresentar uma revisão das referências selecionadas que abordam a detecção precoce de doenças cardiovasculares por meio de imagens de ultrassonografia Doppler. Materiais e Métodos: A busca por artigos científicos foi realizada em bases de dados online e gratuitas, fazendo uso dos Descritores: "Doenças Cardiovasculares"; "Detecção Precoce" e " Ultrassonografia Doppler". Foi realizada uma revisão integrativa, sendo considerados estudos que abordaram os benefícios da Ultrassonografia Doppler no diagnóstico precoce de doencas cardiovasculares. Resultados: A pesquisa de Ribeiro et al. (2015) se concentrou na análise das ondas Doppler de vasos periféricos como uma ferramenta para a detecção de cardiopatias em idosos. Os resultados demonstraram a relevância desse método na identificação precoce de doenças cardiovasculares nessa população específica. Outro estudo relevante foi conduzido por Araújo et al. (2015), que investigou a hemodinâmica cerebral por ultrassonografia Doppler em gestantes com hipertensão arterial crônica. Os resultados evidenciaram a utilidade desse método para o monitoramento da saúde cardiovascular durante a gravidez. As referências selecionadas também abordaram a detecção de alterações cardíacas em diferentes contextos clínicos. De Sousa Franklin et al. (2021) investigaram alterações cardíacas por meio do ecocardiograma fetal e identificaram fatores de risco associados. Já o estudo de Soares et al. (2015) avaliou a acurácia do strain pelo speckle tracking para detecção de fibrose miocárdica em portadores de doença de Chagas. Os estudos incluídos nesta revisão demonstraram a importância da ultrassonografia Doppler na detecção precoce de doenças cardiovasculares. Essa técnica pode fornecer informações valiosas sobre a hemodinâmica vascular, função cardíaca e outros parâmetros relevantes. A detecção precoce possibilita intervenções terapêuticas mais eficazes, resultando em melhores desfechos clínicos para os pacientes. Conclusão: A utilização de imagens de ultrassonografia Doppler tem se mostrado uma abordagem promissora para a detecção precoce de doenças cardiovasculares. A aplicação desses métodos pode contribuir significativamente para a identificação de alterações vasculares e cardíacas, permitindo intervenções precoces e melhorando os resultados clínicos. No entanto, são necessários mais estudos para aprimorar a padronização e o uso clínico dessas técnicas, visando um diagnóstico mais preciso e um manejo mais efetivo das doenças cardiovasculares.
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