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1.
Nutrients ; 13(7)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34371946

RESUMO

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin levels and positively with the jejunal Toll-like receptor (TLR)4, peroxisome proliferator-activated receptor (PPAR)-γ, and interleukin (IL)-10 levels. Furthermore, TAS2R38 expression correlated negatively with TLR9 jejunal expression and IL-6 levels and positively with TLR4 levels. Our findings suggest that metabolic dysfunctions such as MetS trigger downregulation of the intestinal TASs. Therefore, taste receptors modulation could be a possible therapeutic target for metabolic disorders.


Assuntos
Jejuno/metabolismo , Obesidade Mórbida/genética , Receptores Acoplados a Proteínas G/genética , Paladar , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Metabolismo dos Lipídeos/genética , Fígado/patologia , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/patologia , Receptores Acoplados a Proteínas G/metabolismo
2.
Biomed Pharmacother ; 139: 111668, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243630

RESUMO

Metabolic Syndrome (MetS) is a complex and multifactorial condition often characterised by obesity, hypertension, hyperlipidaemia, insulin resistance, glucose intolerance and fasting hyperglycaemia. Collectively, MetS can increase the risk of atherosclerotic-cardiovascular disease, which is the leading cause of death worldwide. However, no animal model currently exists to study MetS in the context of atherosclerosis. In this study we developed a pre-clinical mouse model that recapitulates the spectrum of MetS features while developing atherosclerosis. When BPHx mice were placed on a western type diet for 16 weeks, all the classical characteristics of MetS were observed. Comprehensive metabolic analyses and atherosclerotic imaging revealed BPHx mice to be obese and hypertensive, with elevated total plasma cholesterol and triglyceride levels, that accelerated atherosclerosis. Altogether, we demonstrate that the BPHx mouse has all the major components of MetS, and accelerates the development of atherosclerosis.


Assuntos
Aterosclerose/patologia , Dieta/efeitos adversos , Hipertensão/patologia , Síndrome Metabólica/patologia , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Glicemia/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipertensão/sangue , Hipertensão/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/metabolismo , Obesidade/patologia , Triglicerídeos/sangue
3.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202257

RESUMO

Metabolic syndrome (MetS) is a well-defined yet difficult-to-manage disease entity. Both the precipitous rise in its incidence due to contemporary lifestyles and the growing heterogeneity among affected populations present unprecedented challenges. Moreover, the predisposed risk for developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in populations with MetS, and the viral impacts on host metabolic parameters, underscores the need to investigate this mechanism thoroughly. Recent investigations of metabolomics and proteomics have revealed not only differentially expressed substances in MetS, but also the consequences of diet consumption and physical activity on energy metabolism. These variations in metabolites, as well as protein products, also influence a wide spectrum of host characteristics, from cellular behavior to phenotype. Research on the dysregulation of gut microbiota and the resultant inflammatory status has also contributed to our understanding of the underlying pathogenic mechanisms. As for state-of-the-art therapies, advancing depictions of the bio-molecular landscape of MetS have emerged and now play a key role in individualized precision medicine. Fecal microbiota transplantation, aiming to restore the host's homeostasis, and targeting of the bile acid signaling pathway are two approaches to combatting MetS. Comprehensive molecular inquiries about MetS by omics measures are mandatory to facilitate the development of novel therapeutic modalities.


Assuntos
Síndrome Metabólica/terapia , Animais , COVID-19/patologia , COVID-19/virologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Humanos , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Metabolômica , Medicina de Precisão , Proteômica , SARS-CoV-2/isolamento & purificação
4.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210097

RESUMO

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This study aimed to investigate the effect of PS on obesity and hyperlipidemia in an animal model. Forty male Wistar rats were randomly divided into five experimental groups. The groups were as follows: UG-Untreated group; CTRL-control; FDW-olive oil + 20% fructose; FDW-PS-PS (125 mg/kg) + 20% fructose; FDW-NGN-naringin (100 mg/kg) + 20% fructose. Fructose drinking water was administered daily for 12 weeks ad libitum to induce metabolic abnormality. Treatment was administered at week 8 for four weeks via oral gavage. The rats were sacrificed with anesthesia at the end of the experimental period. Blood, liver, and visceral fat were collected for further analysis. The consumption of 20% fructose water by Wistar rats for eight weeks displayed a tremendous increment in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, leptin, and reduced the levels of HDL and adiponectin as well as adipocyte hypertrophy. Following the treatment period, FDW-PS and FDW-NGN showed a significant reduction in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, and leptin with an increment in the levels of HDL and adiponectin compared to the FDW group. FDW-PS and FDW-NGN also showed adipocyte hypotrophy compared to the FDW group. In conclusion, oral administration of 125 mg/kg PS methanolic extract to fructose-induced obese rats led to significant amelioration of obesity and hyperlipidemia through suppressing the adipocytes and inhibiting HMG-CoA reductase. PS has the potential to be used as an alternative or adjunct therapy for obesity and hyperlipidemia.


Assuntos
Frutose/efeitos adversos , Hiperlipidemias , Síndrome Metabólica , Metanol/química , Obesidade , Piper/química , Extratos Vegetais , Animais , Frutose/farmacologia , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
5.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209700

RESUMO

Disruption of the in utero environment can have dire consequences on fetal growth and development. Intrauterine growth restriction (IUGR) is a pathological condition by which the fetus deviates from its expected growth trajectory, resulting in low birth weight and impaired organ function. The developmental origins of health and disease (DOHaD) postulates that IUGR has lifelong consequences on offspring well-being, as human studies have established an inverse relationship between birth weight and long-term metabolic health. While these trends are apparent in epidemiological data, animal studies have been essential in defining the molecular mechanisms that contribute to this relationship. One such mechanism is cellular stress, a prominent underlying cause of the metabolic syndrome. As such, this review considers the role of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation in the pathogenesis of metabolic disease in IUGR offspring. In addition, we summarize how uncontrolled cellular stress can lead to programmed cell death within the metabolic organs of IUGR offspring.


Assuntos
Suscetibilidade a Doenças , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Estresse Fisiológico , Animais , Apoptose , Biomarcadores , Estresse do Retículo Endoplasmático , Retardo do Crescimento Fetal/diagnóstico , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/metabolismo , Síndrome Metabólica/diagnóstico , Modelos Biológicos , Fosforilação Oxidativa , Estresse Oxidativo , Resposta a Proteínas não Dobradas
6.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206404

RESUMO

Metabolic syndrome (MetS) is a cluster of several disorders, such as hypertension, central obesity, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease. Despite health policies based on the promotion of physical exercise, the reduction of calorie intake and the consumption of healthy food, there is still a global rise in the incidence and prevalence of MetS in the world. This phenomenon can partly be explained by the fact that adverse events in the perinatal period can increase the susceptibility to develop cardiometabolic diseases in adulthood. Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing cardiovascular diseases (CVD) and metabolic disorders later in life. It has been shown that alterations in the structural and functional integrity of the endothelium can lead to the development of cardiometabolic diseases. The endothelial progenitor cells (EPCs) are circulating components of the endothelium playing a major role in vascular homeostasis. An association has been found between the maintenance of endothelial structure and function by EPCs and their ability to differentiate and repair damaged endothelial tissue. In this narrative review, we explore the alterations of EPCs observed in individuals with cardiometabolic disorders, describe some mechanisms related to such dysfunction and propose some therapeutical approaches to reverse the EPCs dysfunction.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Animais , Senescência Celular/efeitos dos fármacos , Gerenciamento Clínico , Suscetibilidade a Doenças , Metabolismo Energético , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/terapia , Especificidade de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Pesquisa Médica Translacional
7.
EBioMedicine ; 69: 103440, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34161887

RESUMO

BACKGROUND: Metabolic syndrome (MetS), a cluster of factors associated with risks of developing cardiovascular diseases, is a public health concern because of its growing prevalence. Considering the combination of concomitant components, their development and severity, MetS phenotypes are largely heterogeneous, inducing disparity in diagnosis. METHODS: A case/control study was designed within the NuAge longitudinal cohort on aging. From a 3-year follow-up of 123 stable individuals, we present a deep phenotyping approach based on a multiplatform metabolomics and lipidomics untargeted strategy to better characterize metabolic perturbations in MetS and define a comprehensive MetS signature stable over time in older men. FINDINGS: We characterize significant changes associated with MetS, involving modulations of 476 metabolites and lipids, and representing 16% of the detected serum metabolome/lipidome. These results revealed a systemic alteration of metabolism, involving various metabolic pathways (urea cycle, amino-acid, sphingo- and glycerophospholipid, and sugar metabolisms…) not only intrinsically interrelated, but also reflecting environmental factors (nutrition, microbiota, physical activity…). INTERPRETATION: These findings allowed identifying a comprehensive MetS signature, reduced to 26 metabolites for future translation into clinical applications for better diagnosing MetS. FUNDING: The NuAge Study was supported by a research grant from the Canadian Institutes of Health Research (CIHR; MOP-62842). The actual NuAge Database and Biobank, containing data and biologic samples of 1,753 NuAge participants (from the initial 1,793 participants), are supported by the Fonds de recherche du Québec (FRQ; 2020-VICO-279753), the Quebec Network for Research on Aging, a thematic network funded by the Fonds de Recherche du Québec - Santé (FRQS) and by the Merck-Frost Chair funded by La Fondation de l'Université de Sherbrooke. All metabolomics and lipidomics analyses were funded and performed within the metaboHUB French infrastructure (ANR-INBS-0010). All authors had full access to the full data in the study and accept responsibility to submit for publication.


Assuntos
Envelhecimento/metabolismo , Síndrome Metabólica/metabolismo , Metaboloma , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Síndrome Metabólica/sangue , Metabolômica/métodos
8.
Mol Cell Biochem ; 476(10): 3827-3844, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34114148

RESUMO

Metabolic syndrome (MetS) is associated with additional cardiovascular risk in mammalians while there are relationships between hyperglycemia-associated cardiovascular dysfunction and increased platelet P2Y12 receptor activation. Although P2Y12 receptor antagonist ticagrelor (Tica) plays roles in reduction of cardiovascular events, its beneficial mechanism remains poorly understood. Therefore, we aimed to clarify whether Tica can exert a direct protective effect in ventricular cardiomyocytes from high-carbohydrate diet-induced MetS rats, at least, through affecting sarcoplasmic reticulum (SR)-mitochondria (Mit) miscommunication. Tica treatment of MetS rats (150 mg/kg/day for 15 days) significantly reversed the altered parameters of action potentials by reversing sarcolemmal ionic currents carried by voltage-dependent Na+ and K+ channels, and Na+/Ca2+-exchanger in the cells, expressed P2Y12 receptors. The increased basal-cytosolic Ca2+ level and depressed SR Ca2+ load were also reversed in Tica-treated cells, at most, though recoveries in the phosphorylation levels of ryanodine receptors and phospholamban. Moreover, there were marked recoveries in Mit structure and function (including increases in both autophagosomes and fragmentations) together with recoveries in Mit proteins and the factors associated with Ca2+ transfer between SR-Mit. There were further significant recoveries in markers of both ER stress and oxidative stress. Taken into consideration the Tica-induced prevention of ER stress and mitochondrial dysfunction, our data provided an important document on the pleiotropic effects of Tica in the electrical activity of the cardiomyocytes from MetS rats. This protective effect seems through recoveries in SR-Mit miscommunication besides modulation of different sarcolemmal ion-channel activities, independent of P2Y12 receptor antagonism.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Carboidratos da Dieta/efeitos adversos , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Retículo Sarcoplasmático/metabolismo , Ticagrelor/farmacologia , Animais , Carboidratos da Dieta/farmacologia , Transporte de Íons/efeitos dos fármacos , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/patologia , Ratos , Ratos Wistar , Retículo Sarcoplasmático/patologia , Transdução de Sinais/efeitos dos fármacos
9.
EMBO Rep ; 22(7): e52036, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34114325

RESUMO

Dysregulation of lipid metabolism could lead to the development of metabolic disorders. We report here that the F-box protein JFK promotes excessive lipid accumulation in adipose tissue and contributes to the development of metabolic syndrome. JFK transgenic mice develop spontaneous obesity, accompanied by dyslipidemia, hyperglycemia, and insulin resistance, phenotypes that are further exacerbated under high-fat diets. In contrast, Jfk knockout mice are lean and resistant to diet-induced metabolic malfunctions. Liver-specific reconstitution of JFK expression in Jfk knockout mice leads to hepatic lipid accumulation resembling human hepatic steatosis and nonalcoholic fatty liver disease. We show that JFK interacts with and destabilizes ING5 through assembly of the SCF complex. Integrative transcriptomic and genomic analysis reveals that the SCFJFK -ING5 axis interferes with AMPK activity and fatty acid ß-oxidation, leading to the suppression of hepatic lipid catabolism. Significantly, JFK is upregulated and AMPKα1 is down-regulated in liver tissues from NAFLD patients. These results reveal that SCFJFK is a bona fide E3 ligase for ING5 and link the SCFJFK -ING5 axis to the development of obesity and metabolic syndrome.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/genética , Obesidade/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
10.
FASEB J ; 35(7): e21665, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34131955

RESUMO

The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), has been suggested to be a key factor in the induction of obesity-associated metabolic dysfunction. However, the role that macrophage-derived TNF-α has on regulating metabolic perturbations in obesity is not completely understood. Therefore, we utilized the TNF-αFlox/Flox (F/F) , LyzMcre± mouse model to determine the impact that macrophage TNF-α deletion has on the development of high-fat diet (HFD)-induced obesity. At 10 weeks of age, male littermates were randomly assigned to 1 of 4 groups: TNF-αF/F low-fat diet (TNF-αF/F LFD), TNF-αF/F, LyzMCre LFD, TNF-αF/F HFD, or TNF-αF/F, LyzMCre HFD (n = 16-28/group) and were fed their respective diets for 18 weeks. Body weight was assessed throughout the course of the experiment. Body composition, hepatic lipid accumulation, and metabolic outcomes were also examined. A microarray gene expression experiment was performed from RNA isolated from epididymal adipose tissue of the HFD-fed groups (n = 10/group) and results were verified via qRT-PCR for all groups. Macrophage-derived TNF-α deletion significantly reduced adipose tissue TNF-α gene expression and circulating TNF-α and downregulated genes linked to the toll-like receptor (TLR) and NFκB signaling pathways. However, macrophage TNF-α deletion had no effect on hindering the development of obesity, hepatic lipid accumulation, or improving glucose metabolism or insulin sensitivity. In conclusion, macrophage-derived TNF-α is not a causative factor for the induction of obesity-associated metabolic dysfunction.


Assuntos
Inflamação/patologia , Resistência à Insulina , Macrófagos/metabolismo , Síndrome Metabólica/patologia , Obesidade/complicações , Fator de Necrose Tumoral alfa/fisiologia , Animais , Dieta Hiperlipídica , Feminino , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout
11.
Molecules ; 26(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063650

RESUMO

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-ß growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)12-luciferase reporter gene assay. CSE also blocked Smad3 phosphorylation induced by MSTN but not by GDF11 or Activin A in Western blot analysis, demonstrating its capacity to block the binding of MSTN to its receptor. Oral administration of CSE significantly increased forelimb muscle mass and grip strength in mice. Using solvent partitioning, solid-phase chromatography, and reverse-phase HPLC, two peaks having MSTN-inhibitory capacity were purified from CSE. The two peaks were identified as ßN-arachinoyl-5-hydroxytryptamide (C20-5HT) and ßN-behenoyl-5-hydroxytryptamide (C22-5HT) using mass spectrometry and NMR analysis. In summary, the results show that CSE has the MSTN-inhibitory capacity, and C20-5HT and C22-5HT are active components of CSE-suppressing MSTN activity, suggesting the potential of CSE, C20-5HT, and C22-5HT being developed as agents to combat muscle atrophy and metabolic syndrome.


Assuntos
Café/metabolismo , Músculo Esquelético/metabolismo , Músculos/efeitos dos fármacos , Miostatina/antagonistas & inibidores , Administração Oral , Animais , Glicemia/análise , Peso Corporal , Osso e Ossos/metabolismo , Etanol , Ácidos Graxos não Esterificados/metabolismo , Concentração Inibidora 50 , Masculino , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/metabolismo , Solventes/química , Fator de Crescimento Transformador beta/metabolismo , Proteína Desacopladora 1/metabolismo
12.
Clin Interv Aging ; 16: 1057-1070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135578

RESUMO

Introduction: The prevalence of metabolic syndrome among the elderly population is growing. The elements of metabolic syndrome in an aging society are currently being researched. Atherosclerosis is a slow process in which the first symptoms may be observed after many years. The mechanisms underlying the progression of atherosclerosis are oxidative stress and inflammation. Inflammation and oxidative stress are associated with the increased incidence of metabolic syndrome. Taking the above into consideration, metabolic syndrome is thought to be a clinical equivalent of atherosclerosis. Aim: The aim of this paper is to review the impact of the interplay of oxidant-antioxidant and inflammation markers in metabolic syndrome in general as well as its components in the pathophysiology which underlies development of atherosclerosis in elderly individuals. Methods: A systematic scan of online resources designed for elderly (≥65 years) published from 2005 to the end of 2020 were reviewed. This was supplemented with grey literature and then all resources were narratively analyzed. The analysis included the following terms: "atherosclerosis or metabolic syndrome" and "oxidative stress or inflammation" and "elderly" to find reports of atherosclerotic disease from asymptomatic to life-threatening among the elderly population with metabolic syndrome . Results: The work summarizes articles that were applicable to this study, including systematic reviews, qualitative studies and opinion pieces. Current knowledge focuses on monitoring the inflammation and oxidant-antioxidant imbalance in disentangling atherosclerosis in patients diagnosed with metabolic syndrome. The population-based studies described inflammation, increased oxidative stress and weak antioxidant defense systems as the mechanisms underlying atherosclerosis development. Moreover, there are discussions that these targets could potentially be a point of intervention to reduce the development of atherosclerosis in the elderly, especially those with altered glucose and lipid metabolism. Specific markers may be used as an approach for the prevention and lifestyle modification of atherosclerotic disease in such population. Conclusion: Metabolic syndrome and its components are important contributors in the progression of atherosclerotic disease in the elderly population but constant efforts should be made to broaden our knowledge of elderly groups who are the most susceptible for the development of atherosclerosis complications.


Assuntos
Antioxidantes/metabolismo , Aterosclerose/metabolismo , Inflamação/metabolismo , Síndrome Metabólica/metabolismo , Oxidantes/metabolismo , Idoso , Envelhecimento/fisiologia , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Humanos , Inflamação/fisiopatologia , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/fisiopatologia , Obesidade/metabolismo , Estresse Oxidativo/fisiologia
13.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071388

RESUMO

Ageing is a complex process which implies the accumulation of molecular, cellular and organ damage, leading to an increased vulnerability to disease. In Western societies, the increase in the elderly population, which is accompanied by ageing-associated pathologies such as cardiovascular and mental diseases, is becoming an increasing economic and social burden for governments. In order to prevent, treat and determine which subjects are more likely to develop these age-related diseases, predictive biomarkers are required. In this sense, some studies suggest that glycans have a potential role as disease biomarkers, as they modify the functions of proteins and take part in intra- and intercellular biological processes. As the glycome reflects the real-time status of these interactions, its characterisation can provide potential diagnostic and prognostic biomarkers for multifactorial diseases. This review gathers the alterations in protein glycosylation profiles that are associated with ageing and age-related diseases, such as cancer, type 2 diabetes mellitus, metabolic syndrome and several chronic inflammatory diseases. Furthermore, the review includes the available techniques for the determination and characterisation of glycans, such as liquid chromatography, electrophoresis, nuclear magnetic resonance and mass spectrometry.


Assuntos
Envelhecimento/metabolismo , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Síndrome Metabólica/metabolismo , Neoplasias/metabolismo , Polissacarídeos/metabolismo , Cromatografia Líquida/métodos , Glicosilação , Humanos , Espectrometria de Massas/métodos
14.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066314

RESUMO

HDL particles can be structurally modified in atherosclerotic disorders associated with low HDL cholesterol level (HDL-C). We studied whether the lipidome of the main phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) species of HDL2 and HDL3 subfractions is associated with premature coronary heart disease (CHD) or metabolic syndrome (MetS) in families where common low HDL-C predisposes to premature CHD. The lipidome was analyzed by LC-MS. Lysophosphatidylcholines were depleted of linoleic acid relative to more saturated and shorter-chained acids containing species in MetS compared with non-affected subjects: the ratio of palmitic to linoleic acid was elevated by more than 30%. A minor PC (16:0/16:1) was elevated (28-40%) in MetS. The contents of oleic acid containing PCs were elevated relative to linoleic acid containing PCs in MetS; the ratio of PC (16:0/18:1) to PC (16:0/18:2) was elevated by 11-16%. Certain PC and SM ratios, e.g., PC (18:0/20:3) to PC (16:0/18:2) and a minor SM 36:2 to an abundant SM 34:1, were higher (11-36%) in MetS and CHD. The fatty acid composition of certain LPCs and PCs displayed a characteristic pattern in MetS, enriched with palmitic, palmitoleic or oleic acids relative to linoleic acid. Certain PC and SM ratios related consistently to CHD and MetS.


Assuntos
Doença da Artéria Coronariana/metabolismo , Ácidos Graxos/metabolismo , Lipoproteínas HDL/metabolismo , Síndrome Metabólica/metabolismo , Fosfolipídeos/metabolismo , Adulto , Família , Feminino , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Fatores de Risco
15.
Eur J Med Chem ; 221: 113535, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992930

RESUMO

Natural products and synthetic analogs have drawn much attention as potential therapeutical drugs to treat metabolic syndrome. We reviewed the underlying mechanisms of 32 natural products and analogs with potential pharmacological effects in vitro, and especially in rodent models and/or patients, that usually act on the PPAR pathway, along with other molecular targets. Recent outstanding total syntheses or semisyntheses of these lead compounds are stated. In general, they can activate the transcriptional activity of PPARα, PPARγ, PPARα/γ, PPARß/δ, PPARα/δ, PPARγ/δ and panPPAR as weak, partial agonists or selective PPARγ modulators (SPPARγM), which may be useful for managing obesity, type 2 diabetes (T2D), dyslipidemia and non-fatty liver disease (NAFLD). Terpenoids is the largest group of compounds that act as potential modulators on PPARs and are comprised from small lipophilic cannabinoids to lipophilic pentacyclic triterpenes and polar saponins. Shikimates-phenylpropanoids include polar heterocyclic flavonoids and phenolic compounds containing at least one C3-C6 unit and usually a double bond on the propyl chain. Quercetin (19), resveratrol (24) and curcumin (27), stand out from this group for exhibiting beneficial effects on patients. Alkaloids, the minor group of potential modulators on PPARs, include berberine (30), which has been widely explored in preclinical and clinical studies for its potential beneficial effects on T2D and dyslipidemia. However, large-scale clinical trials may be warranted for the promising compounds.


Assuntos
Produtos Biológicos/farmacologia , Síndrome Metabólica/tratamento farmacológico , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Animais , Produtos Biológicos/química , Relação Dose-Resposta a Droga , Humanos , Síndrome Metabólica/metabolismo , Estrutura Molecular , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Relação Estrutura-Atividade
16.
FEBS Lett ; 595(13): 1768-1781, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33977527

RESUMO

Transient receptor potential vanilloid subfamily 1 (TRPV1) is a non-selective cation channel protein expressed in neuronal and non-neuronal cells. Although TRPV1 is implicated in thermogenesis and diet-induced obesity (DIO), its precise role remains controversial. TRPV1-/- mice are protected from DIO, while TRPV1 activation enhances thermogenesis to prevent obesity. To reconcile this, we fed wild-type and TRPV1-/- mice for 32 weeks with normal chow or a high-fat diet and analyzed the weight gain, metabolic activities, and thermogenic protein expression in white and brown fats. TRPV1-/- mice became obese, exhibited reduced locomotor activity, reduced energy expenditure, enhanced hepatic steatosis, and decreased thermogenic protein expression in adipose tissues. Our data reveal that lack of TRPV1 does not prevent obesity, but rather enhances metabolic dysfunction.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Redes Reguladoras de Genes/efeitos dos fármacos , Síndrome Metabólica/genética , Obesidade/genética , Canais de Cátion TRPV/genética , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/metabolismo , Camundongos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Termogênese
17.
Life Sci ; 278: 119565, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33965380

RESUMO

More than one hundred RNA modifications decorate the chemical and topological properties of these ribose nucleotides, thereby executing their biological functions through post-transcriptional regulation. In cardiovascular diseases, a wide range of RNA modifications including m6A (N6-adenosine methylation), m5C (5-methylcytidin), Nm (2'-O-ribose-methylation), Ψ (pseudouridine), m7G (N7-methylguanosine), and m1A (N1-adenosine methylation) have been found in tRNA, rRNA, mRNA and other noncoding RNA, which can function as a novel mechanism in metabolic syndrome, heart failure, coronary heart disease, and hypertension. In this review, we will summarize the current understanding of the regulatory roles and significance of several types of RNA modifications in CVDs (cardiovascular diseases) and the interplay between RNA modifications and noncoding RNA, epigenetics. Finally, we will focus on the potential therapeutic strategies by using RNA modifications.


Assuntos
Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Regulação da Expressão Gênica , RNA/metabolismo , Adenosina/metabolismo , Animais , Aterosclerose/metabolismo , Doença das Coronárias/metabolismo , Epigênese Genética , Fibrose/metabolismo , Perfilação da Expressão Gênica , Insuficiência Cardíaca/metabolismo , Humanos , Hipertensão Pulmonar/metabolismo , Hipertrofia , Síndrome Metabólica/metabolismo , Metilação , Camundongos , Microcirculação , Miocárdio/metabolismo , Processamento Pós-Transcricional do RNA , RNA não Traduzido/metabolismo , Regeneração , Traumatismo por Reperfusão , Transcriptoma
18.
Food Funct ; 12(9): 3919-3930, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977963

RESUMO

Metabolic syndrome, which includes a series of metabolic disorders such as hyperglycemia, hyperlipidemia, insulin resistance and obesity, has become a catastrophic disease worldwide. Accordingly, probiotic intervention is a new strategy to alleviate metabolic syndrome, which can adjust the gut microbiota to a certain extent. The aim of the current work was to explore the alleviation of metabolic syndrome by Lactobacillus reuteri and L. rhamnosus. Two L. reuteri and two L. rhamnosus strains were administered to mice with a high-fat diet for 12 weeks. All Lactobacillus strains tested significantly slowed weight gain in the mice. Among four strains, L. reuteri FGSZY33L6 and L. rhamnosus FJSYC4-1 showed the strongest ability to relieve blood glucose disorders, blood lipid disorders, tissue damage, and particularly gut microbiota disorders. Thus, our findings indicate that these strains can regulate the gut microbiota and produce short-chain fatty acids (SCFAs), which can induce satiety hormones, inhibit food intake and increase satiety, and thus improve metabolic syndrome.


Assuntos
Microbioma Gastrointestinal , Lactobacillus reuteri , Lactobacillus rhamnosus , Síndrome Metabólica/terapia , Probióticos , Tecido Adiposo , Animais , Glicemia/análise , Dieta Hiperlipídica , Ingestão de Alimentos , Ácidos Graxos Voláteis/metabolismo , Insulina/sangue , Lipídeos/sangue , Fígado/patologia , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Síndrome Metabólica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Ganho de Peso
19.
Am J Physiol Heart Circ Physiol ; 320(6): H2305-H2312, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33861146

RESUMO

Adults with metabolic syndrome (MetS) have increased fasting arterial stiffness and altered central hemodynamics that contribute, partly, to increased cardiovascular disease (CVD) risk. Although insulin affects aortic wave reflections in healthy adults, the effects in individuals with MetS are unclear. We hypothesized that insulin stimulation would reduce measures of pressure waveforms and hemodynamics in people with MetS. Thirty-five adults with obesity (27 women; 54.2 ± 6.0 yr; 37.1 ± 4.8 kg/m2) were selected for MetS (ATP III criteria) following an overnight fast. Pulse wave analysis was assessed using applanation tonometry before and after a 2-h euglycemic-hyperinsulinemic clamp (90 mg/dL, 40 mU/m2/min). Deconvolution analysis was used to decompose the aortic waveform [augmentation index corrected to heart rate of 75 beats/min (AIx@75); augmentation pressure (AP)] into backward and forward pressure components. Aerobic fitness (V̇o2max), body composition (DXA), and blood biochemistries were also assessed. Insulin significantly reduced augmentation index (AIx@75, 28.0 ± 9.6 vs. 23.0 ± 9.9%, P < 0.01), augmentation pressure (14.8 ± 6.4 vs. 12.0 ± 5.7 mmHg, P < 0.01), pulse pressure amplification (1.26 ± 0.01 vs. 0.03 ± 0.01, P = 0.01), and inflammation [high-sensitivity C-reactive protein (hsCRP): P = 0.02; matrix metallopeptidase 7 (MMP-7): P = 0.03] compared to fasting. In subgroup analyses to understand HTN influence, there were no insulin stimulation differences on any outcome. V̇o2max, visceral fat, and blood potassium correlated with fasting AIx@75 (r = -0.39, P = 0.02; r = 0.41, P = 0.03; r = -0.53, P = 0.002). Potassium levels were also associated with insulin-mediated reductions in AP (r = 0.52, P = 0.002). Our results suggest insulin stimulation improves indices of aortic reflection in adults with MetS.NEW & NOTEWORTHY This study is one of the first to investigate the effects of insulin on central and peripheral hemodynamics in adults with metabolic syndrome. We provide evidence that insulin infusion reduces aortic wave reflection, potentially through a reduction in inflammation and/or via a potassium-mediated vascular response.


Assuntos
Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Insulina/farmacologia , Síndrome Metabólica/fisiopatologia , Análise de Onda de Pulso , Rigidez Vascular/efeitos dos fármacos , Aorta/fisiopatologia , Composição Corporal , Aptidão Cardiorrespiratória , Feminino , Técnica Clamp de Glucose , Hemodinâmica/efeitos dos fármacos , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Consumo de Oxigênio , Rigidez Vascular/fisiologia
20.
Prim Care Diabetes ; 15(4): 629-634, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33849817

RESUMO

BACKGROUND: The epidemiology of COVID-19 and its association with cardiometabolic disorders is poorly understood. This is a narrative review that investigates the effects of COVID-19 infection on insulin resistance in patients with diabetes. METHODS: An online search of all published literature was done via PubMed and Google Scholar using the MeSH terms "COVID-19," "SARS-CoV-2," "coronavirus," "insulin resistance," and "diabetes." Only articles that were directly applicable to insulin resistance in COVID-19 and diabetes was reviewed. RESULTS: Current data shows an increased risk of mortality in patients with diabetes and COVID-19 compared to those without diabetes. COVID-19 triggers insulin resistance in patients, causing chronic metabolic disorders that were non-existent prior to infection. CONCLUSION: Patients with diabetes are more susceptible to COVID-19 infection than those without diabetes. ACE2 expression decreases with infection, exaggerating Ang II activity with subsequent insulin resistance development, an exaggerated immune response and severe SARS-COV-2 infection.


Assuntos
COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Resistência à Insulina , Síndrome Metabólica/epidemiologia , COVID-19/metabolismo , COVID-19/virologia , Comorbidade , Diabetes Mellitus/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Síndrome Metabólica/metabolismo , Síndrome Metabólica/virologia , Prognóstico , Sistema Renina-Angiotensina , Medição de Risco , Fatores de Risco , SARS-CoV-2/patogenicidade
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