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1.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220705

RESUMO

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Assuntos
COVID-19/tratamento farmacológico , Glucocorticoides/efeitos adversos , Insulina/uso terapêutico , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/prevenção & controle , COVID-19/complicações , Cuidados Críticos/métodos , Estado Terminal/terapia , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Glucocorticoides/uso terapêutico , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/mortalidade , Doenças Metabólicas/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/mortalidade , SARS-CoV-2/fisiologia , Resultado do Tratamento
2.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202493

RESUMO

As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess manganese in the body primarily affects the central nervous system, resulting in irreversible neurological disorders. Therefore, to prevent the onset of brain manganese accumulation becomes critical. In this study, we used Zip14-/- mice as a model for ZIP14 deficiency and discovered that these mice were born without manganese loading in the brain, but started to hyper-accumulate manganese within 3 weeks after birth. We demonstrated that decreasing manganese intake in Zip14-/- mice was effective in preventing manganese overload that typically occurs in these animals. Our results provide important insight into future studies that are targeted to reduce the onset of manganese accumulation associated with ZIP14 dysfunction in humans.


Assuntos
Encéfalo/patologia , Proteínas de Transporte de Cátions/deficiência , Dieta , Suscetibilidade a Doenças , Manganês/metabolismo , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Manganês/efeitos adversos , Doenças Metabólicas/patologia , Doenças Metabólicas/prevenção & controle , Camundongos , Especificidade de Órgãos
3.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207143

RESUMO

Epidemiological studies have emphasized the association between a diet rich in fruits and vegetables and a lower frequency of occurrence of inflammatory-related disorders. Black chokeberry (Aronia melanocarpa L.) is a valuable source of biologically active compounds that have been widely investigated for their role in health promotion and cardiovascular disease prevention. Many in vitro and in vivo studies have demonstrated that consumption of these fruits is associated with significant improvements in hypertension, LDL oxidation, lipid peroxidation, total plasma antioxidant capacity and dyslipidemia. The mechanisms for these beneficial effects include upregulation of endothelial nitric oxide synthase, decreased oxidative stress, and inhibition of inflammatory gene expression. Collected findings support the recommendation of such berries as an essential fruit group in a heart-healthy diet. The aim of this review was to summarize the reports on the impact of black chokeberry fruits and extracts against several cardiovascular diseases, e.g., hyperlipidemia, hypercholesterolemia, hypertension, as well as to provide an analysis of the antioxidant and anti-inflammatory effect of these fruits in the abovementioned disorders.


Assuntos
Frutas/química , Photinia/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia
4.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208601

RESUMO

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-ß1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.


Assuntos
Metabolismo dos Carboidratos , Neoplasias Colorretais/metabolismo , Glucose/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Neoplasias Colorretais/complicações , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/terapia , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , Doenças Metabólicas/etiologia , Doenças Metabólicas/prevenção & controle , Fatores de Risco
5.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072788

RESUMO

The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.


Assuntos
Tecido Adiposo/embriologia , Tecido Adiposo/fisiologia , Termogênese , Adipócitos/metabolismo , Adipogenia , Tecido Adiposo Bege/fisiologia , Tecido Adiposo Marrom/fisiologia , Envelhecimento/metabolismo , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , Metabolismo Energético , Epigênese Genética , Regulação da Expressão Gênica , Humanos , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/terapia , Redes e Vias Metabólicas , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/terapia , Organogênese , Termogênese/efeitos dos fármacos , Termogênese/fisiologia
6.
Theriogenology ; 171: 119-129, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052779

RESUMO

Assisted Reproductive Technologies (ART) allowed the births of >8 million babies worldwide. Even if ART children are healthy at birth, several studies reported that ART may cause changes in foetal programming, leading to an increased predisposition to metabolic disorders in adulthood. Previous studies on mouse model showed obesity, glucose intolerance, and hepatic lipid accumulation in ART offspring. A cumulative effect of the different components of ART protocol has been previously described, for example, in the occurrence of epigenetic defects. Here, we investigated whether there is a cumulative effect of embryo transfer (ET), in vitro culture (IVC) and blastomere biopsy (BB) in the onset of metabolic disorders in mouse offspring vs those naturally conceived (Control - CTR). To this aim, proteomic analysis was performed on the livers from adult mouse offspring developed following ET, IVC and BB vs CTR. We observed deregulated expression of proteins involved in lipid, carbohydrate, energy metabolisms and cellular processes in ART offspring. Moreover, we found increased body weight in all ART offspring while i) insulin resistance in BB male, ii) females glucose intolerance and high level of triglycerides and cholesterol in BB females and iii) low levels of interleukin-6 in BB, IVC and ET males. In conclusion, our study suggests that the use of various embryo manipulations influences the metabolic health of adult offspring, resulting in an increased predisposition to hepatic diseases and metabolic syndrome in a sex-specific manner.


Assuntos
Doenças Metabólicas , Doenças dos Roedores , Animais , Fígado , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/veterinária , Camundongos , Proteoma , Proteômica , Técnicas de Reprodução Assistida/veterinária
7.
Chin Med J (Engl) ; 134(11): 1276-1285, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34010200

RESUMO

ABSTRACT: Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.


Assuntos
Frutose , Doenças Metabólicas , Frutose/efeitos adversos , Homeostase , Humanos , Doenças Metabólicas/etiologia
8.
FASEB J ; 35(5): e21596, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33871073

RESUMO

Severe burns remain a leading cause of death and disability worldwide. Despite advances in patient care, the excessive and uncontrolled hypermetabolic stress response induced by this trauma inevitably affects every organ system causing substantial morbidity and mortality. Recent evidence suggests interleukin-6 (IL-6) is a major culprit underlying post-burn hypermetabolism. Indeed, genetic deletion of IL-6 alleviates various complications associated with poor clinical outcomes including the adverse remodeling of adipose tissue, cachexia and hepatic steatosis. Thus, pharmacological blockade of IL-6 may be a more favorable treatment option to fully restore metabolic function after injury. To test this, we investigated the safety and effectiveness of blocking IL-6 for post-burn hypermetabolism using a validated anti-IL-6 monoclonal antibody (mAb) in our experimental murine model. Here, we show daily anti-IL-6 mAb administration protects against burn-induced weight loss (P < .0001) without any adverse effect on mortality. At the organ level, post-burn treatment with the IL-6 blocker suppressed the thermogenic activation of adipose tissue (P < .01) and its associated wasting (P < .05). The reduction of browning-induced lipolysis (P < .0001) indirectly decreased hepatic lipotoxicity (P < .01) which improved liver dysfunction (P < .05). Importantly, the beneficial effects of this anti-IL-6 agent extended to the skin, reflected by the decrease in excessive collagen deposition (P < .001) and genes involved in pathologic fibrosis and scarring (P < .05). Together, our results indicate that post-burn IL-6 blockade leads to significant improvements in systemic hypermetabolism by inhibiting pathological alterations in key immunometabolic organs. These findings support the therapeutic potential of anti-IL-6 interventions to improve care, quality of life, and survival in burned patients.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Anticorpos Monoclonais/farmacologia , Queimaduras/complicações , Fibrose/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Doenças Metabólicas/tratamento farmacológico , Animais , Fibrose/etiologia , Fibrose/patologia , Lipólise , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/patologia , Camundongos , Camundongos Endogâmicos C57BL
9.
Molecules ; 26(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922113

RESUMO

Polyphenols and omega-3 polyunsaturated fatty acids from fish oils, i.e., eicosapentaenoic and docosahexaenoic acids, are well-recognized nutraceuticals, and their single antioxidant and anti-inflammatory properties have been demonstrated in several studies found in the literature. It has been reported that the combination of these nutraceuticals can lead to three-fold increases in glutathione peroxidase activity, two-fold increases in plasma antioxidant capacity, decreases of 50-100% in lipid peroxidation, protein carbonylation, and urinary 8-isoprotanes, as well as 50-200% attenuation of common inflammation biomarkers, among other effects, as compared to their individual capacities. Therefore, the adequate combination of those bioactive food compounds and their single properties should offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human metabolic diseases, frequently diet-induced, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation. However, the certain mechanisms behind their biological activities, in vivo interaction (both between them and other food compounds), and their optimal doses and consumption are not well-known yet. Therefore, we review here the recent evidence accumulated during the last decade about the cooperative action between polyphenols and fish oils against diet-related metabolic alterations, focusing on the mechanisms and pathways described and the effects reported. The final objective is to provide useful information for strategies for personalized nutrition based on these nutraceuticals.


Assuntos
Suplementos Nutricionais , Óleos de Peixe/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Metabolismo Energético , Ácidos Graxos Ômega-3 , Óleos de Peixe/química , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo/efeitos dos fármacos
10.
Nutrients ; 13(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803089

RESUMO

There is growing interest in the potential health-related effects of moderate alcohol consumption and, specifically, of beer. This review provides an assessment of beer-associated effects on cardiovascular and metabolic risk factors to identify a consumption level that can be considered "moderate". We identified all prospective clinical studies and systematic reviews that evaluated the health effects of beer published between January 2007 and April 2020. Five of six selected studies found a protective effect of moderate alcohol drinking on cardiovascular disease (beer up to 385 g/week) vs. abstainers or occasional drinkers. Four out of five papers showed an association between moderate alcohol consumption (beer intake of 84 g alcohol/week) and decreased mortality risk. We concluded that moderate beer consumption of up to 16 g alcohol/day (1 drink/day) for women and 28 g/day (1-2 drinks/day) for men is associated with decreased incidence of cardiovascular disease and overall mortality, among other metabolic health benefits.


Assuntos
Consumo de Bebidas Alcoólicas , Cerveja , Comportamentos Relacionados com a Saúde , Adulto , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Sistema Cardiovascular , Feminino , Humanos , Incidência , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/mortalidade , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Revisões Sistemáticas como Assunto
11.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919065

RESUMO

Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).


Assuntos
Eritrócitos/patologia , Vesículas Extracelulares/patologia , Doenças Metabólicas/patologia , Apneia Obstrutiva do Sono/complicações , Humanos , Doenças Metabólicas/etiologia
12.
Circulation ; 143(19): 1831-1834, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33820441

RESUMO

During the past year, clinicians and the public have been focused on the coronavirus disease 2019 (COVID-19) pandemic and its associated societal and economic effects. However, once the acute phase of this crisis has passed, we will face an enormous wave of death and disability as a result of common chronic diseases (CCDs), with cardiometabolic diseases at the crest (Figure). A tsunami results when an earthquake on the ocean floor creates huge waves that can wreak devastation far distant from the original upheaval, especially when warnings are ignored. Similarly, underlying global and national demographic and risk factor profiles have for some time presaged an overwhelming burden of CCDs. However, although the pandemic has created additional impetus that unless heeded will amplify the consequences of this burden, the rapid adaptations and innovations in care and research prompted by the urgent response to it may also offer us the means to stem this flood.


Assuntos
COVID-19 , Doenças Cardiovasculares , Doenças Metabólicas , Pandemias , SARS-CoV-2 , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/terapia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Doença Crônica , Humanos , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/terapia , Fatores de Risco
13.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804729

RESUMO

Obesity or overweight are not superficial problems, constituting a pressing issue. The obesity index has almost tripled since 1975, which is an alarming state. Most of the individuals are currently becoming overweight or have inappropriate body mass index (BMI) conditions. Obesity is characterized by increased fat accumulation and thus poses a higher health risk. There is increased size and volume of fat cells in the body, which usually accounts for obesity. Many investigations have been carried out in this area, such as behavioral improvements, dietary changes, chemical involvements, etc., but presently no such goals are established to manage these health concerns. Based on previous literature reports and our interpretation, the current review indicates the involvement of various transcriptional and transporter functions in modifying the above-mentioned health conditions. Various transcriptional factors such as Forkhead box O1 (FoxO1) impart a significant effect on the physiology and pathology of metabolic dysfunction such as obesity. FoxO1 plays a dual role whether in the progression or suppression of metabolic processes depending on its targets. Thus, in the current study, will be discussed the dual role of FoxO1 in metabolic conditions (such as obesity), also summarizing the role of various other transcriptional factors involved in obesity.


Assuntos
Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Predisposição Genética para Doença , Obesidade/etiologia , Obesidade/metabolismo , Adipogenia , Animais , Metabolismo Energético , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Insulina/metabolismo , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Obesidade/patologia , Especificidade de Órgãos , Estresse Oxidativo/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
14.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801073

RESUMO

This narrative review discusses the genetics of protection against Helicobacter pylori (Hp) infection. After a brief overview of the importance of studying infectious disease genes, we provide a detailed account of the properties of Hp, with a view to those relevant for our topic. Hp displays a very high level of genetic diversity, detectable even between single colonies from the same patient. The high genetic diversity of Hp can be evaded by stratifying patients according to the infecting Hp strain. This approach enhances the power and replication of the study. Scanning for single nucleotide polymorphisms is generally not successful since genes rarely work alone. We suggest selecting genes to study from among members of the same family, which are therefore inclined to cooperate. Further, extending the analysis to the metabolism would significantly enhance the power of the study. This combined approach displays the protective role of MyD88, TIRAP, and IL1RL1 against Hp infection. Finally, several studies in humans have demonstrated that the blood T cell levels are under the genetic control of the CD39+ T regulatory cells (TREGS).


Assuntos
Resistência à Doença/genética , Patrimônio Genético , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Interações Hospedeiro-Patógeno/genética , Alelos , Animais , Epigênese Genética , Regulação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno/imunologia , Humanos , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Transcrição Genética
15.
Isr Med Assoc J ; 23(4): 245-250, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33899358

RESUMO

BACKGROUND: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM. OBJECTIVES: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics. METHODS: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission. RESULTS: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels. CONCLUSIONS: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.


Assuntos
Cálcio/sangue , Diabetes Mellitus Tipo 2 , Falência Renal Crônica , Magnésio/sangue , Doenças Metabólicas , Idoso , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diuréticos/administração & dosagem , Diuréticos/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos
16.
Front Immunol ; 12: 614429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717101

RESUMO

The worldwide epidemic of metabolic diseases, especially obesity and other diseases caused by it, has shown a dramatic increase in incidence. A great deal of attention has been focused on the underlying mechanisms of these pathological processes and potential strategies to solve these problems. Chronic inflammation initiated by abdominal adipose tissues and immune cell activation in obesity is the major cause of the consequent development of complications. In addition to adipocytes, macrophages and monocytes, natural killer (NK) cells have been verified to be vital components involved in shaping the inflammatory microenvironment, thereby leading to various obesity-related metabolic diseases. Here, we provide an overview of the roles of NK cells and the interactions of these cells with other immune and nonimmune cells in the pathological processes of metabolic diseases. Finally, we also discuss potential therapeutic strategies targeting NK cells to treat metabolic diseases.


Assuntos
Suscetibilidade a Doenças , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Animais , Biomarcadores , Gerenciamento Clínico , Regulação da Expressão Gênica , Humanos , Imunomodulação , Resistência à Insulina , Células Matadoras Naturais/efeitos dos fármacos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/terapia , Terapia de Alvo Molecular , Especificidade de Órgãos , Transdução de Sinais
17.
Acta Diabetol ; 58(7): 845-858, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33723650

RESUMO

AIMS: Previous studies have evaluated long-term metabolic and neurocognitive outcomes in offspring of women with diabetes. However, many studies did not differentiate between different types of diabetes. We aimed to specifically evaluate both metabolic and neurocognitive outcomes in offspring of women with type 1 diabetes mellitus (OT1D). METHODS: We conducted an extensive literature search on PubMed between February 2020 and September 2020. We performed a scoping review including 12 retrospective cohort studies, 15 prospective cohort studies, one case-control study and one cross-sectional study, comparing long-term metabolic and neurocognitive outcomes between OT1D and a control group. RESULTS: OT1D had a higher body mass index and an increased risk for overweight and obesity compared to offspring of mothers without diabetes. A limited number of studies showed a higher risk for (pre)diabetes, higher rates of non-alcoholic fatty liver disease and metabolic syndrome in OT1D. Index offspring had in general similar intelligence and academic achievement as control children but a higher risk for attention deficit and hyperactivity disorders. Data were conflicting concerning the increased risk for autism spectrum disorders. There is limited evidence suggesting that female offspring have more often unfavorable metabolic parameters, while male offspring are more at risk for hyperactivity/impulsivity. CONCLUSION: Maternal type 1 diabetes mellitus is associated with an increased risk of several metabolic complications and neurobehavioral disorders in the offspring. Increased attention for long-term complications in this population is needed. Further research is needed to evaluate whether improved glycemic control in pregnancy can reduce these long-term complications.


Assuntos
Filho de Pais Incapacitados , Diabetes Mellitus Tipo 1 , Gravidez em Diabéticas , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/psicologia , Índice de Massa Corporal , Criança , Filho de Pais Incapacitados/psicologia , Filho de Pais Incapacitados/estatística & dados numéricos , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Obesidade/epidemiologia , Obesidade/etiologia , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco
18.
Eur J Endocrinol ; 184(5): R193-R205, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33630750

RESUMO

During the last decades, it has become clear that the gastrointestinal tract plays a pivotal role in the regulation of glucose homeostasis. More than 40 hormones originate from the gastrointestinal tract and several of these impact glucose metabolism and appetite regulation. An astonishing example of the gut's integrative role in glucose metabolism originates from investigations into bile acid biology. From primary animal studies, it has become clear that bile acids should no longer be labelled as simple detergents necessary for lipid digestion and absorption but should also be recognised as metabolic regulators implicated in lipid, glucose and energy metabolism. The nuclear farnesoid X receptor (FXR) is a part of an exquisite bile acid-sensing system that among other things ensures the optimal size of the bile acid pool. In addition, intestinal and hepatic FXR also impact the regulation of several metabolic processes such as glucose and lipid metabolism. Accordingly, natural and synthetic FXR agonists and certain FXR-regulated factors (i.e. fibroblast growth factor 19 (FGF19)) are increasingly being evaluated as treatments for metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease (and its inflammatory version, non-alcoholic steatohepatitis). Interestingly, decreased FXR activation also benefits glucose metabolism. This can be obtained by reducing bile acid absorption using bile acid sequestering agents (approved for the treatment of type 2 diabetes) or inhibitors of intestinal bile acid transporters,that is the apical sodium-dependent bile acid transporter (ASBT). This article discusses recent clinical trials that provide insights about the role of FXR-FGF19-targetted therapy for the treatment of metabolic diseases.


Assuntos
Doenças Metabólicas/terapia , Terapia de Alvo Molecular/tendências , Receptores Citoplasmáticos e Nucleares/fisiologia , Animais , Ácidos e Sais Biliares/metabolismo , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Terapia de Alvo Molecular/métodos , Receptores Citoplasmáticos e Nucleares/agonistas , Transdução de Sinais/fisiologia
19.
Life Sci ; 271: 119191, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571514

RESUMO

AIMS: Insulin resistance (IR) has become one of the major causative factors for the pathogenesis of various metabolic and neurometabolic diseases. The sedentary lifestyle in association with the consumption of protein-deficient and high-calorie diet results in IR development. This study was aimed to evaluate the neuroprotective effects of Saroglitazar (SGZ), a dual peroxisome-proliferator activated receptor (PPAR-α/γ) in a high fat-low protein diet (HFLPD) fed mouse model of MetS and associated cognitive deficits. METHODS: Adult male C57BL/6J mice were fed with HFLPD plus 15% oral fructose solution for 16 weeks. Starting at the 13th week, SGZ (5 & 10 mg/kg; p.o.) was administered along with HFLPD for four weeks, i.e., the 12th to 16th week of the study groups. Various physiological, serum metabolic, neurobehavioral, neuroinflammatory, and oxidative stress parameters were assessed. The brain histopathology and mRNA expression of diverse genes in specific brain regions were also estimated. RESULTS: The treatment with SGZ at both doses have significantly reversed various HFLPD-induced metabolic and cognitive alterations by improving the glucose and lipid profile in the periphery in addition to the enhanced cerebral glucose homeostasis, BBB integrity, reduced oxidative stress, and neuroinflammation. Furthermore, the SGZ improved locomotion and memory retention while reducing the HFLPD-induced anxiety-like behaviors in the mice. CONCLUSIONS: SGZ treatment showed significant metabo-neuroprotective effects in mice fed with HFLPD, possibly through peripherally mediated activation of PPAR-α/γ and insulin downstream signaling in the cortex and hippocampus.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Dieta com Restrição de Proteínas/efeitos adversos , Doenças Metabólicas/tratamento farmacológico , PPAR alfa/agonistas , PPAR gama/agonistas , Fenilpropionatos/uso terapêutico , Pirróis/uso terapêutico , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/metabolismo , PPAR gama/metabolismo , Fenilpropionatos/farmacologia , Pirróis/farmacologia
20.
Bone Marrow Transplant ; 56(6): 1238-1247, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33441980

RESUMO

Hematopoietic stem cell transplantation (HCT) has been increasingly used for patients with inherited metabolic disorders (IMD). Immune mediated cytopenias (IMCs) after HCT, manifesting as hemolytic anemia, thrombocytopenia, and/or neutropenia, are recognized as a significant complication in this patient population, yet our understanding of the incidence, risk factors, and pathophysiology is currently limited. Review of the published literature demonstrates a higher incidence in younger patients who undergo HCT for a nonmalignant disease indication. However, a few reports suggest that the incidence is even higher among those with IMD (incidence ranging from 10 to 56%). This review summarizes the literature, provides an approach to better understanding of the possible etiology of IMCs, and proposes a diagnostic and management plan for patients with IMD who develop single or multi-lineage cytopenias after HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doenças Metabólicas , Trombocitopenia , Consenso , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Doenças Metabólicas/etiologia , Trombocitopenia/etiologia , Condicionamento Pré-Transplante
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