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1.
PLoS One ; 15(5): e0227720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407314

RESUMO

Numerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erbα) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erbα expression induces muscular atrophy, high adiposity, and metabolic syndrome in mice. Here we show that, unlike knockout mice, Nr1d1 heterozygous mice are not susceptible to muscular atrophy and in fact paradoxically possess larger myofiber diameters and improved neuromuscular function, compared to wildtype mice. Heterozygous mice lacked dyslipidemia, a characteristic of Nr1d1 knockout mice and displayed increased whole-body fatty-acid oxidation during periods of inactivity (light cycle). Heterozygous mice also exhibited higher rates of glucose uptake when fasted, and had elevated basal rates of gluconeogenesis compared to wildtype and knockout littermates. Rev-erbα ablation suppressed glycolysis and fatty acid-oxidation in white-adipose tissue (WAT), whereas partial Rev-erbα loss, curiously stimulated these processes. Our investigations revealed that Rev-erbα dose-dependently regulates glucose metabolism and fatty acid oxidation in WAT and muscle.


Assuntos
Dislipidemias/genética , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Animais , Comportamento Animal/fisiologia , Relógios Circadianos/genética , Dislipidemias/metabolismo , Dislipidemias/patologia , Ácidos Graxos/metabolismo , Gluconeogênese/genética , Glucose/metabolismo , Heterozigoto , Humanos , Metabolismo dos Lipídeos/genética , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Camundongos Knockout , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Miofibrilas/genética , Miofibrilas/metabolismo , Miofibrilas/patologia , Fotoperíodo
2.
Proc Natl Acad Sci U S A ; 117(18): 9840-9850, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32303655

RESUMO

Deregulation of mitochondrial dynamics leads to the accumulation of oxidative stress and unhealthy mitochondria; consequently, this accumulation contributes to premature aging and alterations in mitochondria linked to metabolic complications. We postulate that restrained mitochondrial ATP synthesis might alleviate age-associated disorders and extend healthspan in mammals. Herein, we prepared a previously discovered mitochondrial complex IV moderate inhibitor in drinking water and orally administered to standard-diet-fed, wild-type C57BL/6J mice every day for up to 16 mo. No manifestation of any apparent toxicity or deleterious effect on studied mouse models was observed. The impacts of an added inhibitor on a variety of mitochondrial functions were analyzed, such as respiratory activity, mitochondrial bioenergetics, and biogenesis, and a few age-associated comorbidities, including reactive oxygen species (ROS) production, glucose abnormalities, and obesity in mice. It was found that mitochondrial quality, dynamics, and oxidative metabolism were greatly improved, resulting in lean mice with a specific reduction in visceral fat plus superb energy and glucose homeostasis during their aging period compared to the control group. These results strongly suggest that a mild interference in ATP synthesis through moderation of mitochondrial activity could effectively up-regulate mitogenesis, reduce ROS production, and preserve mitochondrial integrity, thereby impeding the onset of metabolic syndrome. We conclude that this inhibitory intervention in mitochondrial respiration rectified the age-related physiological breakdown in mice by protecting mitochondrial function and markedly mitigated certain undesired primary outcomes of metabolic syndrome, such as obesity and type 2 diabetes. This intervention warrants further research on the treatment of metabolic syndrome of aging in humans.


Assuntos
Envelhecimento/genética , Síndrome Metabólica/metabolismo , Mitocôndrias/genética , Estresse Oxidativo/genética , Trifosfato de Adenosina/biossíntese , Trifosfato de Adenosina/genética , Envelhecimento/metabolismo , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/genética , Glucose/metabolismo , Envelhecimento Saudável/genética , Humanos , Gordura Intra-Abdominal/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Biogênese de Organelas , Espécies Reativas de Oxigênio/metabolismo
3.
PLoS One ; 15(4): e0231927, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343751

RESUMO

Metabolic Syndrome (MS) is characterized by a low-grade inflammatory state causing an alteration of non-invasive indexes derived from blood count, namely monocyte-to-HDL ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). We analyse a population of 771 subjects (394 controls and 377 MS patients) to evaluate the best predictive index of MS. The diagnosis of MS was made according to the 2006 criteria of the International Diabetes Federation (IDF). We performed ROC curve analyses to evaluate the best predictor index of MS. MHR cut-off value was used to classify the population in two different groups and to create the outcome variable of the Recursive Partitioning and Amalgamation (RECPAM) analysis. This method is a tree-structured approach that defines "risk profiles" for each group of dichotomous variables. We showed that MHR index is significantly linked to body mass index (BMI), waist circumference, creatinine, C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR). ROC curve defined an MHR cut-off value of 6.4, which was able to identify two patient groups with significant differences in waist circumference, blood pressure, creatinine, estimated glomerular filtration rate and fasting plasma glucose. RECPAM analysis demonstrated that gender, BMI categorization and hyperglycaemia were the most important risk determinants of increased MHR index that can be considered bona fide a useful and easily obtainable tool to suggest the presence of peculiar metabolic features that predict MS.


Assuntos
Glicemia/análise , Índice de Massa Corporal , Lipoproteínas HDL/sangue , Síndrome Metabólica/patologia , Monócitos/citologia , Adulto , Idoso , Área Sob a Curva , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Curva ROC , Fatores Sexuais , Fumantes , Circunferência da Cintura
4.
Arterioscler Thromb Vasc Biol ; 40(6): 1479-1490, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32268785

RESUMO

OBJECTIVE: Enhanced expression of PAI-1 (plasminogen activator inhibitor-1) has been implicated in atherosclerosis formation in humans with obesity and metabolic syndrome. However, little is known about the effects of pharmacological targeting of PAI-1 on atherogenesis. This study examined the effects of pharmacological PAI-1 inhibition on atherosclerosis formation in a murine model of obesity and metabolic syndrome. Approach and Results: LDL receptor-deficient (ldlr-/-) mice were fed a Western diet high in cholesterol, fat, and sucrose to induce obesity, metabolic dysfunction, and atherosclerosis. Western diet triggered significant upregulation of PAI-1 expression compared with normal diet controls. Addition of a pharmacological PAI-1 inhibitor (either PAI-039 or MDI-2268) to Western diet significantly inhibited obesity and atherosclerosis formation for up to 24 weeks without attenuating food consumption. Pharmacological PAI-1 inhibition significantly decreased macrophage accumulation and cell senescence in atherosclerotic plaques. Recombinant PAI-1 stimulated smooth muscle cell senescence, whereas a PAI-1 mutant defective in LRP1 (LDL receptor-related protein 1) binding did not. The prosenescent effect of PAI-1 was blocked by PAI-039 and R2629, a specific anti-LRP1 antibody. PAI-039 significantly decreased visceral adipose tissue inflammation, hyperglycemia, and hepatic triglyceride content without altering plasma lipid profiles. CONCLUSIONS: Pharmacological targeting of PAI-1 inhibits atherosclerosis in mice with obesity and metabolic syndrome, while inhibiting macrophage accumulation and cell senescence in atherosclerotic plaques, as well as obesity-associated metabolic dysfunction. PAI-1 induces senescence of smooth muscle cells in an LRP1-dependent manner. These results help to define the role of PAI-1 in atherosclerosis formation and suggest a new plasma-lipid-independent strategy for inhibiting atherogenesis.


Assuntos
Aterosclerose/prevenção & controle , Síndrome Metabólica/tratamento farmacológico , Inibidor 1 de Ativador de Plasminogênio/efeitos dos fármacos , Animais , Senescência Celular/efeitos dos fármacos , Dieta Ocidental , Modelos Animais de Doenças , Ácidos Indolacéticos/administração & dosagem , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Síndrome Metabólica/patologia , Síndrome Metabólica/prevenção & controle , Camundongos , Camundongos Knockout , Obesidade/etiologia , Obesidade/prevenção & controle , Placa Aterosclerótica/patologia , Inibidor 1 de Ativador de Plasminogênio/fisiologia , Receptores de LDL/deficiência , Receptores de LDL/genética
5.
Ann Rheum Dis ; 79(5): 646-656, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32205337

RESUMO

OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage. METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability. RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1ß, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations. CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.


Assuntos
Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Síndrome Metabólica/complicações , Osteoartrite do Joelho/terapia , Animais , Biomarcadores/análise , Biópsia por Agulha , Modelos Animais de Doenças , Progressão da Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Meniscos Tibiais/patologia , Meniscos Tibiais/cirurgia , Síndrome Metabólica/patologia , Camundongos Endogâmicos C57BL , Análise Multivariada , Osteoartrite do Joelho/patologia , Distribuição Aleatória , Valores de Referência , Análise de Regressão , Medição de Risco
6.
PLoS One ; 15(2): e0228602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027706

RESUMO

OBJECTIVE: The inflammatory activity of visceral adipose tissue (VAT) is elevated in metabolic syndrome (MS), and associated with vulnerability to atherosclerosis. Inflammation can be assessed by glucose uptake in atherosclerotic plaques. We investigated whether the glucose uptake of VAT, assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), is associated with systemic inflammatory status, and related to the number of MS components. METHODS: 18F-FDG PET/CT was performed in a total of 203 participants: 59 without MS component; M(0), 92 with one or two MS components; M(1-2), and 52 with MS. Glucose uptake in VAT was evaluated using the mean standardized uptake value (SUVmean) and the maximum SUV (SUVmax). Glucose uptakes of immune-related organs such as the spleen and bone marrow (BM) were evaluated using the SUVmax. RESULTS: VAT SUVmax correlated with high-sensitivity C-reactive protein (hsCRP) and the SUVmax of spleen and BM, which reflect the status of systemic inflammation. Both hsCRP and the SUVmax of the spleen and BM were higher in the MS group than in the M(1-2) or M(0) groups. In VAT, SUVmax increased with increasing number of MS components, while SUVmean decreased. CONCLUSIONS: The SUVmax and SUVmean of VAT assessed by 18F-FDG PET/CT reflected inflammation-driven unique glucose metabolism in the VAT of MS patients, distinct from that of atherosclerotic plaques.


Assuntos
Glucose/farmacocinética , Inflamação/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Síndrome Metabólica/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Medula Óssea/metabolismo , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Baço/metabolismo
7.
Diabetes Res Clin Pract ; 161: 108039, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32007512

RESUMO

AIMS: The aim of this study was to investigate whether both weight change and the background intakes of macronutrient modulate the association between dietary branch chain amino acids (BCAAs) and the risk of metabolic syndrome (MetS). METHODS: This prospective study was conducted within the framework of theTehranLipidand Glucose Study. BCAA intakes were collected using a valid and reliable semi-quantitative food frequency questionnaire. MetS components were defined according to the modified national Cholesterol Education Program Adult Treatment Panel III. Weight change was categorized as weight gain (≥ or <7% over 8.9 year follow-up). Dietary fat and carbohydrate intake were categorized as above/below the median intake. RESULTS: Among participants with weight gain ≥ 7% during follow-up, intakes of both dietary BCAAs and its various sources (below or above the median intake) were associated with higher risk of MetS, compared with subjects with lower intakes of BCAAs and weight change ≤ 7%. Background dietary fat and carbohydrate did not modify the association of dietary BCAAs and its various sources with the risk of MetS. CONCLUSIONS: Weight change, but not dietary macronutrient intake, modulates the association between dietary BCAAs and risk of MetS among adults.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Síndrome Metabólica/etiologia , Nutrientes/metabolismo , Ganho de Peso/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
8.
Prostate ; 80(6): 481-490, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32104919

RESUMO

OBJECTIVE: To investigate the potential mechanism of the effect of metabolic syndrome (MetS) on prostate volume (PV) and the risk of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and the relationships of MetS and the major pathogenic factors of MetS with the clinical progression of BPH/LUTS in older Chinese men. SUBJECTS AND METHODS: We analyzed clinical data obtained from 506 ostensibly healthy men who underwent routine health check-ups and recruited 415 subjects from a group of previously studied men after 4 years. We evaluated the associations of major pathological factors of MetS, including insulin resistance, subclinical inflammatory state, and sex hormone changes, with PV, the risk of BPH and the clinical progression of BPH/LUTS by using multiple linear regression and logistic regression. RESULTS: After adjustment for age, insulin, HOMA (homeostatic model assessment) index, leptin, resistin, adiponectin, C-reactive protein, tumor necrosis factor-α (TNF-α), sex hormone-binding globulin, and testosterone levels were significantly associated with PV (all P < .05), and in the age-adjusted logistic regression model, positive associations of resistin and TNF-α with BPH/LUTS were found (OR, 1.662, P = .007 and OR, 1.044, P < .001, respectively). Predictors of BPH/LUTS clinical progression were significantly correlated with MetS and TNF-α. The group with higher TNF-α levels had a higher rate of newly diagnosed BPH (9.5% vs 19.1%, P = .006) and a greater increase in PV levels (0.61 ± 0.08 vs 1.09 ± 0.35 cm3 , P <.001) after 4 years. CONCLUSIONS: MetS and its pathological factors were associated with an increased PV and an increased risk of BPH/LUTS that is more prone to clinical progression. TNF-α may serve as an early biological indicator to identify which patients with BPH/LUTS are at higher risk of unfavorable outcomes.


Assuntos
Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Idoso , Pressão Sanguínea/fisiologia , Humanos , Modelos Logísticos , Masculino , Próstata/metabolismo , Próstata/patologia , Circunferência da Cintura/fisiologia
9.
Curr Cardiol Rev ; 16(2): 153-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32056530

RESUMO

BACKGROUND: In the last two decades, a new phenotype termed Sarcopenic Obesity (SO), in which sarcopenia and obesity coexist, has emerged. OBJECTIVE: The aim of this systematic review and meta-analysis was first to assess the prevalence of Metabolic syndrome (Mets) among individuals with and without SO, and second, to determine if SO may increase the relative risk of Mets. METHODS: This study was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the data were collated by means of metaanalysis and narrative synthesis. RESULTS: Twelve studies including a total of 11,308 adults with overweight or obesity of both genders met the inclusion criteria and were reviewed, revealing two main findings. First, a similar overall prevalence of Mets in individuals with SO (61.49%; 95% CI: 52.19-70.40) when compared to those without SO (56.74%; 95% CI: 47.32-65.93) was identified. Second, the presence of SO appears not to increase the risk of Mets with respect to those without SO (RR = 1.08, 95% CI: 0.99- 1.17, p = 0.07). CONCLUSION: No higher prevalence of Mets among individuals with SO when compared to those with obesity only, nor a significant association between SO and a higher risk of Mets was found.


Assuntos
Síndrome Metabólica/complicações , Obesidade/complicações , Sarcopenia/complicações , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Obesidade/patologia , Prevalência , Fatores de Risco , Sarcopenia/patologia
10.
Muscle Nerve ; 61(4): 475-479, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32012301

RESUMO

INTRODUCTION: This study was conducted to evaluate the association between prediabetes (PD), elements of the metabolic syndrome (MetS), and small fiber neuropathy (SFN). METHODS: A total of 268 patients with SFN symptoms and normal electrophysiology underwent tests to assess small fibers. SFN was diagnosed based on abnormality of at least two among intraepidermal nerve fiber density (IEFND), quantitative sensory testing, and quantitative sudomotor axon reflex testing. RESULTS: There was no difference in IENFD or abnormal skin biopsy frequency between PD and normoglycemia (NG). However, IENFD was lower in people with diabetes mellitus (DM) than in those with NG. An association between HbA1C and IENFD was observed only if DM patients were included. Attributes of the MetS were more common in those with an abnormal skin biopsy but not among those with autonomic dysfunction or meeting SFN criteria. DISCUSSION: DM, but not PD alone, is associated with SFN. Other MetS elements appear to preferentially impact small fiber structure over function.


Assuntos
Axônios/patologia , Diabetes Mellitus/patologia , Síndrome Metabólica/patologia , Condução Nervosa/fisiologia , Estado Pré-Diabético/patologia , Neuropatia de Pequenas Fibras/patologia , Adulto , Idoso , Biópsia , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Estado Pré-Diabético/fisiopatologia , Pele/inervação , Neuropatia de Pequenas Fibras/fisiopatologia
11.
PLoS One ; 15(1): e0227357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910446

RESUMO

Metabolic syndrome (MetS) which is caused by obesity and insulin resistance, is well known for its predictive capability for the risk of type 2 diabetes mellitus and cardiovascular disease. The development of MetS is associated with multiple genetic factors, environmental factors and lifestyle. We performed a genome-wide association study to identify single-nucleotide polymorphism (SNP) related to MetS in large Korean population based samples of 1,362 subjects with MetS and 6,061 controls using the Axiom® Korean Biobank Array 1.0. We replicated the data in another sample including 502 subjects with MetS and 1,751 controls. After adjusting for age and sex, rs662799 located in the APOA5 gene were significantly associated with MetS. 15 SNPs in GCKR, C2orf16, APOA5, ZPR1, and BUD13 were associated with high triglyceride (TG). 14 SNPs in APOA5, ALDH1A2, LIPC, HERPUD1, and CETP, and 2 SNPs in MTNR1B were associated with low high density lipoprotein cholesterol (HDL-C) and high fasting blood glucose respectively. Among these SNPs, 6 TG SNPs: rs1260326, rs1260333, rs1919127, rs964184, rs2075295 and rs1558861 and 11 HDL-C SNPs: rs4775041, rs10468017, rs1800588, rs72786786, rs173539, rs247616, rs247617, rs3764261, rs4783961, rs708272, and rs7499892 were first discovered in Koreans. Additional research is needed to confirm these 17 novel SNPs in Korean population.


Assuntos
HDL-Colesterol/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome Metabólica/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Glicemia/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Genótipo , Humanos , Resistência à Insulina/genética , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologia , Polimorfismo de Nucleotídeo Único
12.
Artigo em Inglês | MEDLINE | ID: mdl-31647994

RESUMO

The mechanisms leading to the low-grade inflammation observed during obesity are not fully understood. Seeking the initiating events, we tested the hypothesis that the intestine could be damaged by repeated lipid supply and therefore participate in inflammation. In mice, 1-5 palm oil gavages increased intestinal permeability via decreased expression and mislocalization of junctional proteins at the cell-cell contacts; altered the intestinal bacterial species by decreasing the abundance of Akkermansia muciniphila, segmented filamentous bacteria, and Clostridium leptum; and increased inflammatory cytokine expression. This was further studied in human intestinal epithelial Caco-2/TC7 cells using the two main components of palm oil, i.e., palmitic and oleic acid. Saturated palmitic acid impaired paracellular permeability and junctional protein localization, and induced inflammatory cytokine expression in the cells, but unsaturated oleic acid did not. Inhibiting de novo ceramide synthesis prevented part of these effects. Altogether, our data show that short exposure to palm oil or palmitic acid induces intestinal dysfunctions targeting barrier integrity and inflammation. Excessive palm oil consumption could be an early player in the gut alterations observed in metabolic diseases.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Síndrome Metabólica/patologia , Óleo de Palmeira/efeitos adversos , Ácido Palmítico/efeitos adversos , Administração Oral , Animais , Células CACO-2 , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/imunologia , Fezes/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Síndrome Metabólica/imunologia , Camundongos , Óleo de Palmeira/administração & dosagem , Óleo de Palmeira/química , Ácido Palmítico/administração & dosagem , Permeabilidade , Junções Íntimas/efeitos dos fármacos
13.
Int J Radiat Biol ; 96(1): 93-99, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561233

RESUMO

Purpose: Growing rates of metabolic syndrome and associated obesity warrant the development of appropriate animal models for better understanding of how those conditions may affect sensitivity to IR exposure.Materials and methods: We subjected male NZO/HlLtJ mice, a strain prone to spontaneous obesity and diabetes, to 0, 5.5, 6.37, 7.4 or 8.5 Gy (137Cs) of total body irradiation (TBI). Mice were monitored for 30 days, after which proximal jejunum and colon tissues were collected for further histological and molecular analysis.Results: Obese NZO/HlLtJ male mice are characterized by their lower sensitivity to IR at doses of 6.37 Gy and under, compared to other strains. Further escalation of the dose, however, results in a steep survival curve, reaching LD100/30 values at a dose of 8.5 Gy. Alterations in the expression of various tight junction-related proteins coupled with activation of inflammatory responses and cell death were the main contributors to the gastrointestinal syndrome.Conclusions: We demonstrate that metabolic syndrome with exhibited hyperglycemia but without alterations to the microvasculature is not a pre-requisite of the increased sensitivity to TBI at high doses. Our studies indicate the potential of NZO/HlLtJ mice for the studies on the role of metabolic syndrome in acute radiation toxicity.


Assuntos
Síndrome Metabólica/etiologia , Lesões por Radiação/etiologia , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Camundongos , Obesidade/complicações , Lesões por Radiação/sangue , Lesões por Radiação/complicações , Lesões por Radiação/patologia , Análise de Sobrevida , Junções Íntimas/efeitos da radiação
14.
Oxid Med Cell Longev ; 2019: 5972575, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827683

RESUMO

Due to the antimetabolic syndrome effect of mulberry and ginger together with the advantages of the synergistic effect and phytosome encapsulation technique, we hypothesized that phytosome containing the combined extracts of mulberry and ginger (PMG) should be able to manage MetS. PMG was developed and assessed the phenolic content and biological activities associated with the pathophysiology of MetS. The antimetabolic syndrome effect and the possible underlying mechanisms in the animal model of MetS were also assessed. Male Wistar rats induced MetS by subjecting to a 16-week high-carbohydrate high-fat diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg/kg for 21 days. They were determined metabolic parameter changes in serum, histomorphology changes of adipose tissue, the inflammatory cytokines such as IL-6 and TNF-α, oxidative stress status, PPAR-γ, and HDAC3 in adipose tissue. Our in vitro data showed that PMG increased phenolic contents and biological activities. PMG significantly improved MetS parameters including body weight gain, lipid profiles, plasma glucose, HOMA-IR, and ACE. In addition, the density and size of adipocyte, adiposity index, and weights of adipose tissues were also improved. Moreover, the decrease in TNF-α and IL-6, oxidative stress status, and HDAC3 expression together with the increase in PPAR-γ expression in adipose tissue was also observed. These data suggest that PMG exhibit antimetabolic syndrome and the possible underlying mechanism may be associated partly with the modulation effect on HDAC3, PPAR-γ, and adipose tissue. In addition, PMG also improves oxidative stress and inflammation in MetS. Therefore, PMG can be served as the potential supplement to manage MetS. However, a clinical trial study is essential to confirm this health benefit.


Assuntos
Gengibre/química , Síndrome Metabólica/patologia , Morus/química , Extratos Vegetais/química , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Antioxidantes/química , Glicemia/análise , LDL-Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Gengibre/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Morus/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795098

RESUMO

Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) risk and plays a role in the development of metabolic syndrome (MetS). In this review, we will discuss the role of EAT in various facets of MetS, including type 2 diabetes mellitus (T2DM) and insulin resistance. We examine the association between EAT and liver steatosis. We also address the correlations of EAT with HIV therapy and with psoriasis. We discuss racial differences in baseline EAT thickness. We conclude that EAT measurement serves as a powerful potential diagnostic tool in assessing cardiovascular and metabolic risk. Measurement of EAT is made less costly, more convenient, and yet accurate and reliable by transthoracic echocardiography. Furthermore, modification of EAT thickness has therapeutic implications for ASCVD, T2DM, and MetS.


Assuntos
Doenças Cardiovasculares/metabolismo , Gordura Intra-Abdominal/metabolismo , Síndrome Metabólica/metabolismo , Pericárdio/metabolismo , Biomarcadores/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Humanos , Gordura Intra-Abdominal/patologia , Metabolismo dos Lipídeos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/patologia , Pericárdio/patologia
16.
PLoS One ; 14(12): e0225893, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31821339

RESUMO

High-intensity interval training (HIIT), is effective to improve cardiorespiratory fitness (CRF) and metabolic syndrome (MetS) components in adults. However, it is unclear if CRF and MetS components respond similarly in men and women after HIIT. For 16 weeks, 63 women (53±7 years) and 56 men (55±8 years) with MetS underwent a three day/week HIIT program. Bodyweight and composition, VO2MAX, surrogate parameters of CRF (Ventilatory threshold (VT), oxygen uptake efficiency slope (OUES) and VE/VCO2 slope), maximal rate of fat oxidation (MFO), and MetS components were assessed before and after training. All reported variables were analyzed by split-plot ANOVA looking for time by sex interactions. Before training men had higher absolute values of VO2MAX (58.6%), and MFO (24.6%), while lower body fat mass (10.5%) than women (all P<0.05). After normalization by fat-free mass (FFM), VO2MAX remained 16.6% higher in men (P<0.05), whereas differences in MFO disappeared (P = 0.292). After intervention VO2MAX (P<0.001), VO2 at VT (P<0.001), OUES (P<0.001), and VE/VCO2 slope (P<0.001) increased without differences by sex (P>0.05). After training MetS Z-score (P<0.001) improved without differences between men and women (P>0.05). From the MetS components, only blood pressure (P<0.001) and waist circumference (P<0.001) improved across time, without differences by sex. In both, women and men, changes in OUES (r = 0.685 and r = 0.445, respectively), and VO2 at VT (r = 0.378, and r = 0.445, respectively), correlated with VO2MAX. While only bodyweight changes correlated with MetS Z-score changes (r = 0.372, and = 0.300, respectively). Despite baseline differences, 16-weeks of HIIT similarly improved MetS, cardiorespiratory and metabolic fitness in women and men with MetS. This suggests that there are no restrictions due to sex on the benefits derived from an intense exercise program in the health of MetS participants. Trial Registration: clinicaltrials.gov NCT03019796.


Assuntos
Terapia por Exercício , Treinamento Intervalado de Alta Intensidade , Síndrome Metabólica , Adulto , Idoso , Peso Corporal , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/terapia , Pessoa de Meia-Idade , Fatores de Tempo , Circunferência da Cintura
17.
Lipids Health Dis ; 18(1): 229, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881889

RESUMO

BACKGROUND: Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. METHODS: We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. RESULTS: A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28-2.57, p < 0.01), elevated fasting blood glucose (FBG) (OR = 1.43, 95% CI 1.00-2.07, p = 0.05) and hypertension grades (OR = 1.20, 95% CI 1.00-1.44, p = 0.05) were associated with the prevalence of CKD. In sub-group analysis, elevated TG remained strongly associated with CKD in both diabetes (OR = 2.10, 95%CI 1.22-3.61, p < 0.01) and non-diabetes (OR = 1.53, 95% CI 1.09-2.16, p = 0.01). In sub-group analysis of hypertension grades, there was also a graded trend between elevated TG and CKD from controlled blood pressure (BP) to hypertension grade 2 (OR = 1.81, 95%CI 1.06-3.11, p = 0.03; OR = 1.85, 95%CI 1.00-3.43, p = 0.05; OR = 2.81, 95% CI 1.09-7.28, p = 0.03, respectively). CONCLUSION: Elevated TG, elevated FBG and hypertension grades were significantly associated with the prevalence of CKD in patients with hypertension. Particularly, elevated TG was strongly associated with CKD, independent of diabetes and hypertension grades.


Assuntos
Hipertensão/sangue , Síndrome Metabólica/sangue , Insuficiência Renal Crônica/sangue , Triglicerídeos/sangue , Idoso , Glicemia , Pressão Sanguínea , Complicações do Diabetes/sangue , Complicações do Diabetes/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/patologia , Modelos Logísticos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/patologia , Fatores de Risco
18.
Stem Cell Res Ther ; 10(1): 392, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847882

RESUMO

BACKGROUND: Chondrogenesis represents a highly dynamic cellular process that leads to the establishment of various types of cartilage. However, when stress-related injuries occur, a rapid and efficient regeneration of the tissues is necessary to maintain cartilage integrity. Mesenchymal stem cells (MSCs) are known to exhibit high capacity for self-renewal and pluripotency effects, and thus play a pivotal role in the repair and regeneration of damaged cartilage. On the other hand, the influence of certain pathological conditions such as metabolic disorders on MSCs can seriously impair their regenerative properties and thus reduce their therapeutic potential. OBJECTIVES: In this investigation, we attempted to improve and potentiate the in vitro chondrogenic ability of adipose-derived mesenchymal stromal stem cells (ASCs) isolated from horses suffering from metabolic syndrome. METHODS: Cultured cells in chondrogenic-inductive medium supplemented with Cladophora glomerata methanolic extract were experimented for expression of the main genes and microRNAs involved in the differentiation process using RT-PCR, for their morphological changes through confocal and scanning electron microscopy and for their physiological homeostasis. RESULTS: The different added concentrations of C. glomerata extract to the basic chondrogenic inductive culture medium promoted the proliferation of equine metabolic syndrome ASCs (ASCsEMS) and resulted in chondrogenic phenotype differentiation and higher mRNA expression of collagen type II, aggrecan, cartilage oligomeric matrix protein, and Sox9 among others. The results reveal an obvious inhibitory effect of hypertrophy and a strong repression of miR-145-5p, miR-146-3p, and miR-34a and miR-449a largely involved in cartilage degradation. Treated cells additionally exhibited significant reduced apoptosis and oxidative stress, as well as promoted viability and mitochondrial potentiation. CONCLUSION: Chondrogenesis in EqASCsEMS was found to be prominent after chondrogenic induction in conditions containing C. glomerata extract, suggesting that the macroalgae could be considered for the enhancement of ASC cultures and their reparative properties.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Clorófitas/química , Condrogênese/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Síndrome Metabólica/patologia , Extratos Vegetais/farmacologia , Agrecanas/genética , Agrecanas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Clorófitas/metabolismo , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Cavalos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Síndrome Metabólica/metabolismo , MicroRNAs/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/fisiologia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo
19.
Vopr Pitan ; 88(4): 18-24, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31722137

RESUMO

Among various food proteins, soybean proteins have the greatest traditions of application for the dietary correction and prevention of lipid metabolism disorders and related complications. Aim. In an in vivo experiment using male Wistar rats, the lipid-lowering properties of soy protein and its enzymatic hydrolysate were tested to evaluate their possible use as ingredients of specialized foods. Material and methods. Animals were randomly divided into 3 groups: control group G1 and 2 experimental groups G2 and G3. The total duration of the experiment was 70 days. The animals of the control group G1 were fed with high-lipid semi-synthetic diet. Animals of the experimental groups G2 and G3 received the same high-fat semi-synthetic diet, but with a 50% replacement of casein with soy protein isolate (SPI) and enzymatic hydrolyzate of SPI (EHSPI), respectively. The blood glucose was measured once per 2 weeks. At the end of the experiment on the 71st day the level of glycated hemoglobin was determined in the blood; the levels of triglycerides, cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL) and the concentration of malon dialdehyde were determined in the serum. Results and discussion. Starting from the 6th week of the experiment and prior to its completion, the average food intake of animals from the G3 group was significantly (р<0.05) lower compared to animals of the G1 control group. The food intake of animals of group G2 was significantly (р<0.05) reduced compared with this indicator for animals of group G1, starting from the week 8 of the experiment and prior to its completion. The monitoring of the body weight gain did not reveal significant differences between all groups of animals, despite differences in the food intake. Replacing casein in the diet by 50% with SPI had a pronounced antioxidant and cholesterol-lowering effect. The total cholesterol content (1.65±0.05 mmol/l) decreased significantly (р<0.05) due to a decrease in LDL (0.90±0.03 mmol/l), and malon dialdehyde level lowered (3.7±0.5 µmol/l, р<0.05) in the serum of group G2 rats compared with animals of the control group G1 (2.01±0.13 and 1.12±0.09 mmol/l; 5.1±0.4 µmol/l, respectively). Replacing casein by 50% with EHSPI in the diet of G3 rats was unfavorable, significantly (р<0.05) increasing the level of total cholesterol (2.76±0.16 mmol/l) and cholesterol in LDL (1.66±0.12 mmol/l) in blood of these animals compared with animals of both comparison groups G1 and G2. Conclusion. A preclinical comparative study of the cholesterol-lowering and antioxidant properties of the SPI substantiates the prospect of its following clinical trials with the aim of including into the composition of specialized foods for prevention and diet therapy of the disorders of endogenous cholesterol homeostasis.


Assuntos
Gorduras na Dieta/efeitos adversos , Síndrome Metabólica , Obesidade , Hidrolisados de Proteína/farmacologia , Proteínas de Soja/farmacologia , Animais , Gorduras na Dieta/farmacologia , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Obesidade/induzido quimicamente , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/patologia , Ratos , Ratos Wistar
20.
Biochemistry (Mosc) ; 84(11): 1329-1345, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760921

RESUMO

Obesity is a major risk factor for type 2 diabetes and metabolic syndrome and an essential medical and social problem. In the first part of the review, we briefly highlight the biochemical basis of metabolic disbalance in obesity and evolution of our views on the mechanisms of insulin resistance development in insulin-sensitive tissues. Because obesity relates to the disturbance in the normal physiology of fat tissue, the second part of the review focuses on latent inflammation that develops in obesity and is supported by immune cells. Finally, the problem of adipocyte hypertrophy, reduced regenerative potential of fat progenitor cells, and impaired renewal of fat depots is discussed in the context of type 2 diabetes pathogenesis.


Assuntos
Inflamação/patologia , Resistência à Insulina , Obesidade/patologia , Adipogenia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Inflamação/metabolismo , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Obesidade/complicações , Obesidade/metabolismo
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