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1.
Nutr. hosp ; 36(5): 1095-1100, sept.-oct. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-184632

RESUMO

Introducción: el principal problema de salud pública en México es la obesidad y sus enfermedades asociadas, incluyendo las bucales. Objetivo: evaluar el efecto del tratamiento con metformina en pacientes obesos de clase I sobre la actividad de las metaloproteinasas presentes en el periodonto con periodontitis crónica. Métodos: se realizó un estudio clínico con 68 pacientes mujeres con obesidad de clase I y enfermedad periodontal. Se dividieron en 4 grupos; a 2 de ellos, además del tratamiento periodontal, se les administro metformina de 850 mg al día durante seis semanas. Se tomaron 2 muestras por paciente de tejido periodontal antes y después de cada tratamiento y se midió el índice de masa corporal (IMC), el índice de placa dentobacteriana y de inflamación. Mediante zimografía en gel de acrilamida se midió la actividad de las metaloproteinasas en la muestra de tejido recolectada. Los datos obtenidos fueron analizados mediante estadística descriptiva t de student para muestras relacionadas y se realizó ANOVA de una vía considerando p < 0,01 como estadísticamente significativa. Resultados: en el grupo de pacientes a las que se les administro metformina al final del tratamiento se observó una disminución del índice de masa corporal, del grado de inflamación y menor actividad de metaloproteinasas respecto al grupo control (65% frente a 25%; p < 0,01). Conclusiones: el tratamiento con metformina en pacientes con obesidad de clase I y enfermedad periodontal disminuye el IMC, mejora los síntomas de la periodontitis crónica y disminuye la actividad de las metaloproteinasas 1, 3, 8 y V presentes en el periodonto de estos pacientes


Introduction: in Mexico the main problem in public health is obesity and other diseases that are associated whit this condition, including oral health. Objective: to evaluate the effect of metformin treatment in patients with class I obese on the activity of metalloproteinases present in periodontium with chronic periodontitis. Methods: a clinical study was conducted in 68 patients with class I obesity and periodontal disease. They were divided into 4 groups. 2 of them, in addition to the periodontal treatment, were administered metformin 850 mg per day for six weeks; 2 samples were taken per patient of periodontal tissue before and after each treatment, body mass index, plaque index and inflammation were measured. Acrylamide gel zymography was used to measure the activity of metalloproteinases in the sample of tissue collected. The data obtained were analyzed by descriptive statistics, student t for related samples and one-way ANOVA was performed considering p < 0.01 as statistically significant. Results: in the group of patients who were administered metformin at the end of the treatment, there was a decrease in the body mass index, the degree of inflammation and lower metalloproteinase activity, compared with the control group (65% vs 25%; < 0.01). Conclusions: treatment with metformin in patients with obesity class I and periodontal disease decreases BMI, improves the symptoms of chronic periodontitis and decreases the activity of metalloproteinases 1, 3, 8, V present in periodontium of these patients


Assuntos
Humanos , Feminino , Adulto , Obesidade/tratamento farmacológico , Obesidade/enzimologia , Metformina/administração & dosagem , Metaloproteases/metabolismo , Periodontite/complicações , Periodontite/diagnóstico , Metformina/metabolismo , Periodontite/terapia , Análise de Variância , Placa Dentária/diagnóstico , Índice de Placa Dentária
2.
Nutrients ; 11(9)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510106

RESUMO

Nowadays, obesity and its complications are heavy burdens to western civilization. Surgical procedures remain one of the available therapies for obesity and obesity-associated diseases treatment. Among them, sleeve gastrectomy is the most common bariatric procedure. Despite the well-established fact that sleeve gastrectomy results in significant weight loss, some of its other divergent effects still need to be established. To fulfill this knowledge gap, we examined whether sleeve gastrectomy affects lipid metabolism in the plasma and liver of obese rats. We demonstrated that chronic high-fat diet feeding led to an increment in the level of Proprotein Convertase Subtilisin/Kexin (PCSK)-a regulator of plasma cholesterol concentration-in the liver, which was decreased after the gastrectomy. Moreover, we noticed significant increases in both plasma and liver contents of free fatty acids, diacylgycerides and triacylglycerides in the obese animals, with their reduction after the bariatric surgery. In conclusion, we revealed, presumably for the first time, that sleeve gastrectomy affects lipid metabolism in the liver of obese rats.


Assuntos
Gastrectomia , Lipídeos/sangue , Fígado/enzimologia , Obesidade/cirurgia , Pró-Proteína Convertase 9/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Masculino , Obesidade/sangue , Obesidade/enzimologia , Ratos Wistar , Perda de Peso
3.
Mol Cell ; 76(3): 500-515.e8, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31422874

RESUMO

Diet-induced obesity can be caused by impaired thermogenesis of beige adipocytes, the brown-like adipocytes in white adipose tissue (WAT). Promoting brown-like features in WAT has been an attractive therapeutic approach for obesity. However, the mechanism underlying beige adipocyte formation is largely unknown. N-α-acetyltransferase 10 protein (Naa10p) catalyzes N-α-acetylation of nascent proteins, and overexpression of human Naa10p is linked to cancer development. Here, we report that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, and beige adipocyte differentiation. Mechanistically, Naa10p acetylates the N terminus of Pgc1α, which prevents Pgc1α from interacting with Pparγ to activate key genes, such as Ucp1, involved in beige adipocyte function. Consistently, fat tissues of obese human individuals show higher NAA10 expression. Thus, Naa10p-mediated N-terminal acetylation of Pgc1α downregulates thermogenic gene expression, making inhibition of Naa10p enzymatic activity a potential strategy for treating obesity.


Assuntos
Adipócitos Bege/enzimologia , Tecido Adiposo Bege/enzimologia , Acetiltransferase N-Terminal A/metabolismo , Acetiltransferase N-Terminal E/metabolismo , Obesidade/enzimologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Processamento de Proteína Pós-Traducional , Termogênese , Acetilação , Tecido Adiposo Bege/fisiopatologia , Adiposidade , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo Energético , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Acetiltransferase N-Terminal A/deficiência , Acetiltransferase N-Terminal A/genética , Acetiltransferase N-Terminal E/deficiência , Acetiltransferase N-Terminal E/genética , Células NIH 3T3 , Obesidade/genética , Obesidade/fisiopatologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fenótipo , Transdução de Sinais , Adulto Jovem
4.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443565

RESUMO

Obesity is a global health threat. Herein, we evaluated the underlying mechanism of anti-obese features of bitter orange (Citrus aurantium Linné, CA). Eight-week-administration of CA in high fat diet-induced obese C57BL/6 mice resulted in a significant decrease of body weight, adipose tissue weight and serum cholesterol. In further in vitro studies, we observed decreased lipid droplets in CA-treated 3T3-L1 adipocytes. Suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha indicated CA-inhibited adipogenesis. Moreover, CA-treated primary cultured brown adipocytes displayed increased differentiation associated with elevation of thermogenic factors including uncoupling protein 1 and PPARγ coactivator 1 alpha as well. The effects of CA in both adipocytes were abolished in AMP-activated protein kinase alpha (AMPKα)-suppressed environments, suggesting the anti-adipogenic and pro-thermogenic actions of CA were dependent on AMPKα pathway. In conclusion, our results suggest CA as a potential anti-obese agent which regulates adipogenesis and thermogenesis via AMPKα.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Citrus , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Termogênese/efeitos dos fármacos , Células 3T3-L1 , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/enzimologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/enzimologia , Tecido Adiposo/enzimologia , Tecido Adiposo/fisiopatologia , Animais , Fármacos Antiobesidade/isolamento & purificação , Citrus/química , Modelos Animais de Doenças , Ativação Enzimática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/enzimologia , Obesidade/fisiopatologia , Extratos Vegetais/isolamento & purificação , Transdução de Sinais
5.
Life Sci ; 232: 116638, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288013

RESUMO

AIMS: High-fat diet (HFD)-induced obesity resulting in cholesterol accumulation is one of the common pathogenic factors for lipids metabolic disorders. However, the potential mechanisms about cholesterol accumulation during obesity are still not clearly identified. Bile acids (BAs) as the natural ligands of farnesoid x receptor (Fxr) are demonstrated that can regulate the relevant enzymes and transporters at transcriptional level to determine the cholesterol homeostasis. Here, we explored the underlying mechanisms of hepatic cholesterol accumulation in HFD-induced obesity rats via the BAs-Fxr-enzymes/transporters signaling pathways. MATERIALS AND METHODS: BAs and cholesterol levels as well as mRNA expressions of enzymes, transporters and nuclear receptors involving in cholesterol homeostasis in liver and ileum tissue were evaluated in 4-week HFD-induced obesity rats. KEY FINDINGS: HFD promoted BAs intestine passive absorption to increase the concentrations of BAs especially the chenodeoxycholic acids (CDCAs) in ileum of HFD-induced obesity rats. The increased CDCAs concentrations activated Fxr-Fgf15 pathway in ileum to result in the mRNA expression of Cyp7a1 in liver down-regulation, which inhibited cholesterol metabolizing into primary BAs to contribute to the cholesterol level increase in liver tissue in HFD-induced obesity rats. SIGNIFICANCE: The hepatic cholesterol accumulation should be ascribed to the activation of ileum Fxr-Fgf15 pathway by the increased BAs passive absorption into ileal enterocytes under the condition of rats fed with HFD, which inhibited hepatic Cyp7a1 gene transcription to reduce metabolic elimination of cholesterol. Moreover, these findings are expected to provide a cue for the treatment of cholesterol metabolism disorders in obesity patient.


Assuntos
Colesterol 7-alfa-Hidroxilase/antagonistas & inibidores , Dieta Hiperlipídica , Fatores de Crescimento de Fibroblastos/metabolismo , Íleo/metabolismo , Fígado/metabolismo , Obesidade/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Células CACO-2 , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Humanos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Obesidade/enzimologia , Ratos , Ratos Wistar , Transdução de Sinais
6.
Nutrients ; 11(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340540

RESUMO

Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Dieta Hiperlipídica , Hipotálamo/enzimologia , Leptina/metabolismo , Liases/deficiência , Neurônios/metabolismo , Obesidade/prevenção & controle , Tecido Adiposo Marrom/enzimologia , Tecido Adiposo Marrom/fisiopatologia , Adiposidade , Animais , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Hipotálamo/fisiopatologia , Liases/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/enzimologia , Obesidade/genética , Obesidade/fisiopatologia , Transdução de Sinais , Proteína Desacopladora 1/metabolismo , Ganho de Peso
7.
J Physiol Biochem ; 75(3): 321-327, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31290115

RESUMO

Oxidative stress-related inflammation is known to play a vital role in obesity-associated cardiovascular disease, contributing to the early stages of the pathology as well as during its development. Therefore, it is of great interest to understand how obesity-induced stress modulates antioxidant enzyme activity during puberty. To this end, 27 severely obese adolescents (body mass index > 30, z-score > 3.7) were recruited from a paediatric weight management centre. Eighteen were recruited during the summer and nine in the winter. All underwent a 4-month weight loss programme consisting in diet and physical activity. Twenty normal-weight age-matched adolescents were recruited from the same geographical area to serve as controls. Blood samples were extracted, and antioxidant enzyme activities were determined in peripheral blood mononuclear cells (PBMCs) and erythrocytes. The enzymes studied included catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Severely obese adolescents presented lower PBMC-glutathione reductase activity than their corresponding normal-weight counterparts. In addition, glutathione-dependent activities tended to be lower in both groups during the winter compared with summer. These changes coincided with differences in circulating vitamin D levels. Results may suggest that season-dependent factors such as vitamin D could affect glutathione-dependent activities in severely obese as well as in normal-weight adolescents.


Assuntos
Enzimas/sangue , Obesidade/enzimologia , Adolescente , Feminino , Humanos , Masculino , Estações do Ano
8.
Vopr Pitan ; 88(3): 63-68, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31265776

RESUMO

The results of experimental studies indicate that the preventive and therapeutic effects of polyphenols in obesity are accompanied by a significant decrease in the severity of dysbiosis caused by the predominance of fats and simple carbohydrates in the diet, especially fructose, and the restoration of the functional state of the microbiota. The aim of the work was to study the effect of quercetin and resveratrol - polyphenols, widely represented in the daily human diet, on the activity of bacterial glycosidases in rats receiving diets high in fructose or fat and fructose. Material and methods. Using spectrophotometric analysis, the activity of ß-galactosidase (Gal), ß-glucosidase (Glu) and ß-glucuronidase (Gluс) was studied in the content of the cecum of Wistar rats receiving a semi-synthetic diet and a 20% solution of fructose instead of drinking water (hfr diet) or a semi-synthetic diet with a high (30%) fat content and a 20% solution of fructose instead of drinking water (hf/hfr diet). Results and discussion. Feeding rats with the hfr diet for 20 weeks led to the suppression of Gal activity by 35, Glu by 46 and Gluс by 31%. With the inclusion of quercetin in the hfr diet at a dose of 34 mg/kg b.w. enzyme activity was restored to the control values and exceeded the level of activity in rats fed hfr ration without quercetin by 60, 100 and 47%, respectively, for Gal, Glu, and Gluс. Feeding rats with the hf/hfr diet for 10 weeks did not have a significant impact on the activity of bacterial enzymes. The inclusion of resveratrol in the hf/hfr diet at a dose of 10 mg/kg b.w. resulted in a decrease in Glu activity by 58 and Gluс by 28%, and an increase in resveratrol dose to 100 mg/kg b.w. caused further suppression of Gal activity by 30, Glu by 76 and Gluc by 64% comparative to the activity in rats on the hf/hfr diet without resveratrol. Conclusion. The obtained data suggest that quercetin restores reduced by hfr diet activity of glycosyl hydrolases of the cecum microflora of rats, most likely due to an increase in the representation of the types of enzyme activity carriers. The suppressive effect of resveratrol on the activity of glycosyl hydrolases of the cecum microflora of rats fed a hf/hfr diet may be the result of its direct action on enzymes and is not associated with the effect on the composition of the intestinal microbiota.


Assuntos
Proteínas de Bactérias/metabolismo , Ceco , Carboidratos da Dieta/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Glicosídeo Hidrolases/metabolismo , Obesidade , Polifenóis/farmacologia , Animais , Ceco/enzimologia , Ceco/microbiologia , Carboidratos da Dieta/farmacologia , Frutose/efeitos adversos , Frutose/farmacologia , Masculino , Obesidade/induzido quimicamente , Obesidade/enzimologia , Obesidade/microbiologia , Quercetina/farmacologia , Ratos , Ratos Wistar , Resveratrol/farmacologia
9.
Am J Gastroenterol ; 114(6): 916-928, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31169533

RESUMO

INTRODUCTION: Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels. METHODS: We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured. RESULTS: LSM was better than both FIB-4 and NFS for staging F3-F4 fibrosis area under the receiver operating characteristic curve test (AUC) 0.863, 0.777, and 0.765, respectively; P < 0.001 for both), showing higher accuracy and higher negative predictive value (NPV), but lower positive predictive value (PPV). LSM worked less well in high ALT (>100 IU) (AUC 0.811 vs 0.877, P = 0.04; PPV 57.5% vs 62.4%; NPV 90.7% vs 94%) or obese patients (AUC 0.786 vs 0.902, P < 0.001; PPV 58.7% vs 64.8%; NPV 88.3% vs 95.2%), the latter not being affected by the M or XL probe. Consistently, LSM worked better in terms of AUC and accuracy compared with both FIB-4 and NFS only in nonobese or high ALT patients, even with always keeping a slightly lower PPV. A serial combination of FIB-4 or NFS with LSM as the second test in patients in the gray area of the first test retained-in most scenarios-similar PPV and NPV compared with LSM alone. These strategies also increased the diagnostic accuracy of about 20% in all groups of patients, even if with a lower overall accuracy in obese patients (71.3% and 67.1% for FIB-4 and NFS as the first test, respectively) compared to nonobese patients (81.9% and 82.4% for FIB-4 and NFS as the first test, respectively). CONCLUSIONS: All tested noninvasive tools have overall better NPV than PPV. LSM has a better diagnostic accuracy for advanced fibrosis than both FIB-4 and NFS only in nonobese and/or low ALT patients. Serial combination strategies are better than a single tool strategy, regardless of obesity and ALT levels, although the accuracy is lower in obese patients.


Assuntos
Alanina Transaminase/sangue , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/etiologia , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/complicações , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Feminino , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/enzimologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/enzimologia , Obesidade/enzimologia , Valor Preditivo dos Testes , Curva ROC , Índice de Gravidade de Doença
10.
Can J Physiol Pharmacol ; 97(9): 844-849, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31051081

RESUMO

Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms. Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study was conducted to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production, quantitative real-time PCR, and immunohistology studies. The human visceral adipose tissue and mesenteric artery branches contain mainly the MAO-A isoform, as shown by the quantitative real-time PCR and immunohistology experiments. A significant upregulation of MAO-A, the impairment in vascular reactivity, and increase in ROS production were found in obese vs. non-obese patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominant isoform in human abdominal adipose and vascular tissues, is overexpressed in the setting of inflammation, and contributes to the endothelial dysfunction.


Assuntos
Monoaminoxidase/metabolismo , Obesidade/metabolismo , Estresse Oxidativo , Adulto , Idoso , Doença Crônica , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Inflamação/complicações , Gordura Intra-Abdominal/metabolismo , Masculino , Artérias Mesentéricas/metabolismo , Pessoa de Meia-Idade , Monoaminoxidase/genética , Obesidade/complicações , Obesidade/enzimologia , Obesidade/genética , Espécies Reativas de Oxigênio/metabolismo
11.
Am J Clin Nutr ; 109(4): 1029-1037, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982860

RESUMO

BACKGROUND: Several studies recently reported contradicting results regarding the link between amylase 1 (AMY1) copy numbers (CNs), obesity, and type 2 diabetes. OBJECTIVE: The aim of this study was to assess the impact of AMY1 CN on anthropometrics and glycemic outcomes in obese individuals following a 2-phase dietary weight loss intervention. METHODS: Using the paralog ratio test, AMY1 CNs were accurately measured in 761 obese individuals from the DiOGenes study. Subjects first underwent an 8-wk low-calorie diet (LCD, at 800 kcal/d) and then were randomly assigned to a 6-mo weight maintenance dietary (WMD) intervention with arms having different glycemic loads. RESULTS: At baseline, a modest association between AMY1 CN and BMI (P = 0.04) was observed. AMY1 CN was not associated with baseline glycemic variables. In addition, AMY1 CN was not associated with anthropometric or glycemic outcomes following either LCD or WMD. Interaction analyses between AMY1 CN and nutrient intake did not reveal any significant association with clinical parameters (at baseline and following LCD or WMD) or when testing gene × WMD interactions during the WMD phase. CONCLUSION: In the absence of association with weight trajectories or glycemic improvements, the AMY1 CN cannot be considered as an important biomarker for response to a clinical weight loss and weight maintenance programs in overweight/obese subjects. This trial was registered at www.clinicaltrials.gov as NCT00390637.


Assuntos
Obesidade/dietoterapia , Obesidade/genética , alfa-Amilases Salivares/genética , Adulto , Peso Corporal , Trajetória do Peso do Corpo , Restrição Calórica , Feminino , Dosagem de Genes , Carga Glicêmica , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/enzimologia , Obesidade/fisiopatologia , alfa-Amilases Salivares/metabolismo , Perda de Peso
12.
Int J Mol Sci ; 20(4)2019 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-30813483

RESUMO

Initially reported as a longevity-related protein, the 66 kDa isoform of the mammalian Shc1 locus has been implicated in several metabolic pathways, being able to act both as an adaptor protein and as a redox enzyme capable of generating reactive oxygen species (ROS) when it localizes to the mitochondrion. Ablation of p66Shc has been shown to be protective against obesity and the insurgence of insulin resistance, but not all the studies available in the literature agree on these points. This review will focus in particular on the role of p66Shc in the modulation of glucose homeostasis, obesity, body temperature, and respiration/energy expenditure. In view of the obesity and diabetes epidemic, p66Shc may represent a promising therapeutic target with enormous implications for human health.


Assuntos
Resistência à Insulina , Obesidade/enzimologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Animais , Metabolismo Energético , Humanos , Oxirredução , Transdução de Sinais
13.
NMR Biomed ; 32(6): e4085, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30920054

RESUMO

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kf CK ) for healthy volunteers and obese patients. TRiST measures kf CK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kf CK measurement during <20 min of dobutamine stress. We test our TRiST implementation in skeletal muscle and myocardium in both prone and supine positions. We evaluate StreST in the myocardium of six healthy volunteers and 34 obese subjects. We validated MR-measured kf CK against biopsy assays of CK activity. TRiST kf CK values matched literature values in skeletal muscle (kf CK  = 0.25 ± 0.03 s-1 vs 0.27 ± 0.03 s-1 ) and myocardium when measured in the prone position (0.32 ± 0.15 s-1 ), but a significant difference was found for TRiST kf CK measured supine (0.24 ± 0.12 s-1 ). This difference was because of different respiratory- and cardiac-motion-induced B0 changes in the two positions. Using supine TRiST, cardiac kf CK values for normal-weight subjects were 0.15 ± 0.09 s-1 at rest and 0.17 ± 0.15 s-1 during stress. For obese subjects, kf CK was 0.16 ± 0.07 s-1 at rest and 0.17 ± 0.10 s-1 during stress. Rest myocardial kf CK and CK activity from LV biopsies of the same subjects correlated (R = 0.43, p = 0.03). We present an independent implementation of TRiST on the Siemens platform using a commercially available coil. Our extended StreST protocol enables cardiac kf CK to be measured during dobutamine-induced stress in the supine position.


Assuntos
Creatina Quinase/metabolismo , Coração/fisiopatologia , Espectroscopia de Ressonância Magnética , Descanso , Estresse Fisiológico , Adulto , Biópsia , Estudos de Casos e Controles , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Obesidade/enzimologia , Obesidade/fisiopatologia , Postura , Reprodutibilidade dos Testes , Respiração
14.
Nutr Metab Cardiovasc Dis ; 29(4): 409-420, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30799179

RESUMO

BACKGROUND AND AIM: Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity. METHODS AND RESULTS: Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA. CONCLUSIONS: The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Metabolismo Energético/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/prevenção & controle , Triterpenos/farmacologia , Células 3T3-L1 , Adipócitos/enzimologia , Adipócitos/patologia , Adiposidade/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Ativação Enzimática , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/enzimologia , Obesidade/patologia , Obesidade/fisiopatologia , Fosforilação , Transdução de Sinais , Ganho de Peso/efeitos dos fármacos
15.
Am J Physiol Renal Physiol ; 316(5): F889-F897, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30810354

RESUMO

Sex is an important biological variable that impacts diverse physiological and pathological processes, including the progression of diabetic nephropathy. Diabetic nephropathy is one of the most common complications of diabetes mellitus and is the leading cause of end-stage renal disease. The endothelial nitric oxide synthase-deficient (eNOS-/-) db/db mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy because of the similarities of the features of diabetic kidney disease in this model to those in humans. The aim of the present study was to determine whether there was a sex difference in renal injury in eNOS-/- db/db mice. Both male and female eNOS-/- db/db mice showed hyperglycemia, obesity, and renal hypertrophy. However, there was no significant difference in those variables between male and female mice. Furthermore, both male and female diabetic mice showed progressive albuminuria and significantly greater levels of serum creatinine and blood urea nitrogen compared with the same sex of wild-type mice (nondiabetic controls). Although all three variables in female eNOS-/- db/db mice had a tendency to be greater than those in male eNOS-/- db/db mice, those sex differences were not statistically significant. Moreover, both male and female eNOS-/- db/db mice showed significant mesangial expansion, higher glomerular injury scores, profound renal fibrosis, and substantial accumulation of fibronectin and collagen type IV proteins. However, sex differences in those structural changes were not observed. Similarly, survival rates of male and female eNOS-/- db/db mice were comparable. Taken together, the results from the present study suggest no sex difference in renal structural and functional damage in eNOS-/- db/db mice.


Assuntos
Nefropatias Diabéticas/enzimologia , Rim/enzimologia , Óxido Nítrico Sintase Tipo III/deficiência , Animais , Glicemia/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Proteínas da Matriz Extracelular/metabolismo , Feminino , Fibrose , Predisposição Genética para Doença , Hiperglicemia/sangue , Hiperglicemia/enzimologia , Hiperglicemia/genética , Rim/patologia , Rim/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/genética , Obesidade/enzimologia , Obesidade/genética , Obesidade/fisiopatologia , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Fatores Sexuais , Micção , Ganho de Peso
16.
Arch Physiol Biochem ; 125(5): 423-429, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29898610

RESUMO

Objective: To evaluate the effect of the administration of phytoestrogens on obesity, type 2 diabetes, and liver-kidney toxicity. Methods: Phytoestrogens (phyto(E2)) were administrated to high fructose-fat diet (HFFD). Results: This study showed that administration of phyto(E2) to HFFD-mice inhibited lipase activity by 34%, decreased body weight by 20% and modulated lipid profile, showed a decrease in total-cholesterol (TC) and LDL-cholesterol (LDL-C) rates in the plasma by 59% and 42%, respectively, and increased the HDL-cholesterol (HDL-C) level by 31%. In addition, the administration of phytoestrogens to HFFD-mice exerts an inhibitory effect on α-amylase activity and decreased glucose level by 28% and increase in liver glycogen level by 33%; and ameliorate oral glucose tolerance test. Conclusions: This study demonstrate that phyto(E2) has both a promising potential with regards to the inhibition of intestinal lipase and α-amylase activities, and a valuable hypoglycemic and hypolipidemic function.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Dieta Hiperlipídica/efeitos adversos , Frutose/efeitos adversos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Obesidade/enzimologia , Fitoestrógenos/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glicogênio/metabolismo , Rim/enzimologia , Rim/metabolismo , Rim/fisiopatologia , Lipase/antagonistas & inibidores , Lipídeos/sangue , Fígado/enzimologia , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Camundongos
17.
Eur J Clin Invest ; 49(1): e13036, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30316201

RESUMO

Copper-zinc superoxide dismutase (Cu,Zn-SOD) plays a protective role in various types of tissue protecting them from oxidative damage. Alterations in Cu,Zn-SOD (SOD1 and SOD3) activity and its expression have been observed in pathological occurrences most prevalent in modern society, including inflammatory bowel disease, obesity and its implications-diabetes and hypertension, and chronic obstructive pulmonary disease. Moreover, several SOD1 and SOD3 gene polymorphisms have been associated with the risk of developing a particular type of disease, or its exacerbation. This article features recent observations in this topic, aiming to show the importance of proper gene sequence and activity of Cu,Zn-SOD in the aforementioned diseases.


Assuntos
Diabetes Mellitus/enzimologia , Doenças Inflamatórias Intestinais/enzimologia , Obesidade/enzimologia , Doença Pulmonar Obstrutiva Crônica/enzimologia , Superóxido Dismutase-1/metabolismo , Antioxidantes/fisiologia , Doença Crônica , Humanos , Oxirredução
18.
Diab Vasc Dis Res ; 16(2): 160-170, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30295509

RESUMO

Insulin and insulin-like growth factor-1 stimulate specific responses in arteries, which may be disrupted by diet-induced obesity. We examined (1) temporal effects of high-fat diet compared to low-fat diet in mice on insulin receptor, insulin-like growth factor-1 receptor, insulin receptor/insulin-like growth factor-1 receptor hybrid receptor expression and insulin/insulin-like growth factor-1-mediated Akt phosphorylation in aorta; and (2) effects of high-fat diet on insulin and insulin-like growth factor-1-mediated Akt phosphorylation and vascular tone in resistance arteries. Medium-term high-fat diet (5 weeks) decreased insulin-like growth factor-1 receptor expression and increased hybrid expression (~30%) only. After long-term (16 weeks) high-fat diet, insulin receptor expression was reduced by ~30%, insulin-like growth factor-1 receptor expression decreased a further ~40% and hybrid expression increased a further ~60%. Independent correlates of hybrid receptor expression were high-fat diet, duration of high-fat diet and plasma insulin-like growth factor-1 (all p < 0.05). In aorta, insulin was a more potent activator of Akt than insulin-like growth factor-1, whereas in resistance arteries, insulin-like growth factor-1 was more potent than insulin. High-fat diet blunted insulin-mediated vasorelaxation ( p < 0.01) but had no effect on insulin-like growth factor-1-mediated vasorelaxation in resistance arteries. Our findings support the possibility that hybrid receptor level is influenced by nutritional and metabolic cues. Moreover, vessel-dependent effects of insulin and insulin-like growth factor-1 on vascular tone and Akt activation may have implications in treating obesity-related vascular disease.


Assuntos
Aorta/efeitos dos fármacos , Insulina/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Obesidade/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Resistência Vascular/efeitos dos fármacos , Animais , Antígenos CD/metabolismo , Aorta/enzimologia , Células Cultivadas , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Modelos Animais de Doenças , Ativação Enzimática , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Masculino , Artérias Mesentéricas/enzimologia , Artérias Mesentéricas/fisiopatologia , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/fisiopatologia , Fosforilação , Receptor IGF Tipo 1/genética , Receptor de Insulina/metabolismo , Receptores de Somatomedina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
19.
Prog Lipid Res ; 73: 28-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30472260

RESUMO

12/15-lipoxygenase (12/15-LOX) is an enzyme, which oxidizes polyunsaturated fatty acids, particularly omega-6 and -3 fatty acids, to generate a number of bioactive lipid metabolites. A large number of studies have revealed the importance of 12/15-LOX role in oxidative and inflammatory responses. The in vitro studies have demonstrated the ability of 12/15-LOX metabolites in the expression of various genes and production of cytokine related to inflammation and resolution of inflammation. The studies with the use of knockout and transgenic animals for 12/15-LOX have further shown its involvement in the pathogenesis of a variety of human diseases, including cardiovascular, renal, neurological and metabolic disorders. This review summarizes our current knowledge on the role of 12/15-LOX in inflammation and various human diseases.


Assuntos
Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/metabolismo , Inflamação/enzimologia , Animais , Animais Geneticamente Modificados , Araquidonato 12-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/genética , Complicações do Diabetes/enzimologia , Complicações do Diabetes/patologia , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Humanos , Inflamação/patologia , Doenças do Sistema Nervoso/enzimologia , Doenças do Sistema Nervoso/patologia , Obesidade/enzimologia , Obesidade/patologia , Doenças Vasculares/enzimologia , Doenças Vasculares/patologia
20.
Food Chem Toxicol ; 123: 443-452, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30408537

RESUMO

Rubus grandifolius Lowe (wild blackberries) is an endemic species from Madeira Archipelago (Portugal) used in folk medicine for alleviating diabetic complications. In this work, R. grandifolius methanolic extracts were analysed for in vitro inhibitory effect on digestive enzymes linked to type-2 diabetes, as well as aldose reductase activity and protein glycation. The phenolic composition, antioxidant and cytotoxic activities were also determined. Methanolic extracts exhibited strong inhibition of glucosidases (α- and ß), but were less potent for α-amylase and pancreatic lipase when compared to current pharmaceutical drugs. The total phenolic content determined by HPLC-DAD varied between 92.96 - 97.47 and 118.01-137.41 mg g-1 of dry extract for berries and leaves, respectively. Fifty polyphenols were quantified, anthocyanins and ellagitannins being the main compounds. Cyanidin-3-glucoside was identified as one of the main hypoglycaemic and hypolipidemic agents in all extracts. R. grandifolius also prevented glycation of bovine-serum albumin (BSA) and showed strong radical scavenging activity against tested free radicals. At low concentration, the extracts were not cytotoxic against Caco-2 cells. Based on the results of this study, wild blackberry extracts demonstrated a potential beneficial effect on the control/management of type-2 diabetes mellitus, validating their use in folk medicine.


Assuntos
Fármacos Antiobesidade/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Rubus/química , Fármacos Antiobesidade/química , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Flavonoides/farmacologia , Frutas/química , Humanos , Hipoglicemiantes/química , Obesidade/enzimologia , Obesidade/metabolismo , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo
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