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1.
Braz. j. biol ; 83: e251198, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1339350

ABSTRACT

Abstract The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.


Resumo O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.


Subject(s)
Animals , Rats , Asteraceae , Antioxidants , DNA Damage , Plant Extracts/pharmacology , Rats, Wistar , Obesity/drug therapy
2.
Arq. bras. cardiol ; 117(4): 715-725, Oct. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1345249

ABSTRACT

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.


Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.


Subject(s)
Animals , Mice , Receptors, Chemokine , Diabetes Mellitus, Experimental/drug therapy , Carnitine/pharmacology , Chemokines , Intercellular Signaling Peptides and Proteins , Mice, Obese , Obesity/drug therapy
3.
Chinese Medical Journal ; (24): 2882-2889, 2021.
Article in English | WPRIM | ID: wpr-921201

ABSTRACT

BACKGROUND@#Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.@*METHODS@#Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.@*RESULTS@#Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.@*CONCLUSIONS@#COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.


Subject(s)
Exenatide/therapeutic use , Female , Humans , Metformin/therapeutic use , Obesity/drug therapy , Overweight , Polycystic Ovary Syndrome/drug therapy
4.
Arq. bras. cardiol ; 115(1): 17-28, jul. 2020. tab, graf
Article in Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1131262

ABSTRACT

Resumo Fundamento A obesidade tem sido associada com ativação crônica do sistema renina-angiotensina-aldosterona e importantes alterações no desempenho cardíaco. Objetivo Avaliar a influência do bloqueio de receptores de angiotensina-II do tipo 1 (AT1) sobre a morfologia e desempenho cardíaco de ratos obesos por dieta Métodos Ratos Wistar (n=48) foram submetidos a dieta controle (2,9 kcal/g) ou hiperlipídica (3,6 kcal/g) durante 20 semanas. Após a 16ª semana, foram distribuídos em quatro grupos: Controle (CO), Obeso (OB), Controle Losartan (CL) e Obeso Losartan (OL). CL e OL receberam losartan (30 mg/kg/dia) na água durante quatro semanas. Posteriormente, foram analisadas composição corporal, pressão arterial sistólica (PAS) e ecocardiograma. A função de músculos papilares foi avaliada em situação basal com concentração de cálcio ([Ca2+]o) de 2,50 mM e após manobras inotrópicas: potencial pós-pausa (PPP), elevação da [Ca2+]o e durante estimulação beta-adrenérgica com isoproterenol. A análise dos resultados foi feita por meio de Two-Way ANOVA e teste de comparações apropriado. O nível de significância considerado foi de 5%. Resultados Embora a alteração da PAS não tenha se mantido ao final do experimento, a obesidade se associou com hipertrofia cardíaca e maior velocidade de encurtamento da parede posterior do ventrículo esquerdo.No estudo de músculos papilares em condição basal, CL mostrou menor velocidade máxima de variação negativa da tensão desenvolvida (-dT/dt) do que CO. O PPP de 60s promoveu menor -dT/dt e pico de tensão desenvolvida (TD) em OB e CL, comparados ao CO, e maior variação relativa de TD e velocidade máxima de variação positiva (+dT/dt) no OL em relação a CL e OB. Sob 1,5, 2,0 e 2,5mM de [Ca2+]o, o grupo OL exibiu maior -dT/dt do que CL. Conclusão Losartan melhora a função miocárdica de ratos com obesidade induzida por dieta. (Arq Bras Cardiol. 2020; 115(1):17-28)


Abstract Background Obesity has been associated with chronic activation of the renin-angiotensin-aldosterone system and with significant changes in cardiac performance. Objective To assess the impact of a blockade of angiotensin-II receptor type 1 (AT1receptor) on morphology and on myocardial functional performance in rats with high-fat diet- induced obesity. Methods Wistar rats (n=48) were submitted to control (2.9 kcal/g) or high-fat (3.6 kcal/g) diet for 20 weeks. After the 16thweek they were divided into four groups: Control (CO), Obese (OB), Control Losartan (CL) and Obese Losartan (OL). CL and OL received losartan (30 mg/kg/day) in drinking water for four weeks. Subsequently, body composition, systolic blood pressure (SBP) and echocardiographic variables were analyzed. Papillary muscle function was assessed at baseline with 2.50 mM calcium concentration ([Ca2+]o) and after inotropic maneuvers: post-pause potentiation (PPP), [Ca2+]oelevation, and during beta-adrenergic stimulation with isoproterenol. Analysis of the results was performed by the Two-Way ANOVA and by the appropriate comparison test. The level of significance was set at 5%. Results Although SBP change had been not maintained at the end of the experiment, obesity was associated with cardiac hypertrophy and with increased left ventricle posterior wall shortening velocity. In the study of papillary muscles in basal condition, CL showed lower developed tension maximum negative variation velocity (-dT/dt) than CO. The 60s PPP promoted lower -dT/dt and maximum developed tension (DT) in OB and CL compared with CO, and higher relative DT variation and maximum positive variation velocity (+dT/dt) in OL compared with CL and OB. Under 1.5, 2.0, and 2.5mM [Ca2+]o, the OL group showed higher -dT/dt than CL. Conclusion Losartan improves myocardial function in high-fat diet-induced obesity. (Arq Bras Cardiol. 2020;115(1):17-28)


Subject(s)
Animals , Rats , Diet, High-Fat/adverse effects , Obesity/drug therapy , Papillary Muscles , Rats, Wistar , Physical Functional Performance , Myocardial Contraction
5.
Einstein (Säo Paulo) ; 18: eAO4876, 2020. tab, graf
Article in English | LILACS | ID: biblio-1039734

ABSTRACT

ABSTRACT Objective To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. Methods Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. Results Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. Conclusion Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.


RESUMO Objetivo Investigar os efeitos da sericina extraída de casulos de Bombyx mori na morfofisiologia de camundongos com obesidade induzida por dieta hiperlipídica. Métodos Camundongos machos C57Bl6, com 9 semanas de idade, foram distribuídos em Grupos Controle e Obeso, que receberam ração padrão para roedores ou dieta hiperlipídica por 10 semanas, respectivamente. Posteriormente, os animais foram redistribuídos em quatro grupos, com sete animais cada: Controle, Controle-Sericina, Obeso e Obeso-Sericina. Os animais permaneceram recebendo ração padrão ou hiperlipídica por 4 semanas, período no qual a sericina foi administrada oralmente na dose de 1.000mg/kg de massa corporal aos Grupos Controle-Sericina e Obeso-Sericina. Parâmetros fisiológicos, como ganho de peso, consumo alimentar, peso das fezes em análise de lipídios fecais, motilidade intestinal e tolerância à glicose foram monitorados. Ao término do experimento, o plasma foi coletado para dosagens bioquímicas e fragmentos de tecido adiposo branco; fígado e jejuno foram processados para análises histológicas, e amostras hepáticas foram usadas para determinação lipídica. Resultados Camundongos obesos apresentaram ganho de peso e acúmulo de gordura significativamente maior que os controles, aumento do colesterol total e glicemia. Houve hipertrofia dos adipócitos retroperitoneais e periepididimais, instalação de esteatose e aumento do colesterol e triglicerídeos hepáticos, bem como alteração morfométrica da parede jejunal. Conclusão O tratamento com sericina não reverteu todas as alterações fisiológicas promovidas pela obesidade, mas restaurou a morfometria jejunal e aumentou a quantidade de lipídios eliminados nas fezes dos camundongos obesos, apresentando-se como potencial tratamento para a obesidade.


Subject(s)
Animals , Male , Anti-Obesity Agents/therapeutic use , Sericins/therapeutic use , Obesity/drug therapy , Time Factors , Triglycerides/analysis , Body Weight/drug effects , Gastrointestinal Transit/drug effects , Weight Gain/drug effects , Adipose Tissue/pathology , Cholesterol/analysis , Reproducibility of Results , Treatment Outcome , Anti-Obesity Agents/pharmacology , Sericins/pharmacology , Eating/drug effects , Fatty Liver/pathology , Diet, High-Fat/adverse effects , Glucose Tolerance Test , Liver/metabolism , Mice, Inbred C57BL , Mice, Obese , Obesity/etiology , Obesity/physiopathology
6.
Braz. arch. biol. technol ; 62: e19180563, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039120

ABSTRACT

Abstract The objective of this study was to evaluate the effect of liraglutide, an analog of glucagon-like peptide-1 (GLP-1) in association with physical exercise, on the metabolic and biochemical parameters of rats induced to obesity with a cafeteria diet. Male Wistar rats, aged 21 days, were randomly divided into: Controls (CON) receiving standard feed and water ad libitum; and obese (OBESE) receiving cafeteria diet ad libitum, added to the standard diet. Groups were then subdivided into: Liraglutide animals that received subcutaneous injections of liraglutide from 80 to 90 days of life; exercised (EXE) animals submitted to swimming sessions, three days a week (15 min); and liraglutide + EXE animals that received liraglutide in association with physical exercise. Treatment with liraglutide reduced deposits of mesenteric and periepididymal fat, HOMA-IR, triglycerides, glucose and insulin in obese group. It is important to note that the association of the two treatments reduced the body weight in animals, deposits of mesenteric and periepididymal fat, HOMA-IR, blood triglyceride levels, glucose and insulin in obese rats. As such, the association of liraglutide with exercise potentiated the effects of the drug and ameliorated obesity pathology more effectively. retirar


Subject(s)
Animals , Metabolic Syndrome , Liraglutide/therapeutic use , Motor Activity , Obesity/drug therapy , Rats, Wistar
8.
Rev. ciênc. farm. básica apl ; 3901/01/2018. tab, ilus
Article in English | LILACS | ID: biblio-1100210

ABSTRACT

The safety and effectiveness of main anti-obesity drugs are controversial, and there is no consensus among regulatory agencies regarding anti-obesity drugs. We undertook an overview of systematic reviews (SR) of randomized controlled trials (RCT) to summarize the quality of evidence related to anti-obesity drugs. Data sources included Medline, Scopus, The Cochrane Library and PROSPERO. Twenty-one SR (564 RCT; average of 2,356 participants per review) satisfied the inclusion criteria. Ten SR presented a high level of heterogeneity, and only five SR included sensitivity analyses. The most important limitations reported by the SR were a high level of attrition, a small sample size, and a short follow-up. Eight different outcomes for efficacy were used, 15 different outcomes for biomarkers were used, and nine different outcomes for safety were used. Conclusions: In conclusion, the quality of SR pertaining to anti-obesity drugs is low, and these reviews have a high level of heterogeneity. Future SR should present more detailed population inclusion criteria, larger sample sizes, and focus variables reported in a predefined anti-obesity core outcome set.(AU)


Subject(s)
Humans , Anti-Obesity Agents/therapeutic use , Evidence-Based Practice , Obesity/drug therapy , Treatment Outcome , Systematic Reviews as Topic
9.
Medwave ; 18(6): e7288, 2018.
Article in English, Spanish | LILACS | ID: biblio-948404

ABSTRACT

Resumen Introducción Las enfermedades crónicas van en ascenso y están asociadas al incremento ponderal. Se requieren estrategias multidisciplinarias para su control. Métodos El diseño es descriptivo, observacional y retrospectivo. Los objetivos de esta comunicación son describir las características demográficas, clínicas y reacciones adversas de personas con sobrepeso y obesidad consumidores de orlistat, atendidos por un centro de atención telefónica durante el periodo 2009 a 2017; e identificar al profesional de la salud más consultado por ellos. La información se obtuvo desde una base de datos existente de un programa de atención a personas con sobrepeso u obesidad, interesadas en usar orlistat (prospectos) o usuarios (pacientes). El estudio se llevó a cabo en México y duró siete años. Las variables estudiadas fueron demográficas, clínicas y reacciones adversas. Resultados Se reunieron 311 913 solicitudes de 126 607 sujetos (104 711 prospectos interesados en consumir orlistat y 21 896 pacientes que ya lo tomaban). Las principales actividades fueron llamadas al sujeto (35,9%). Hubo 104 711 solicitudes: 82 810 (79,1%) prospectos y 21 896 (20,9%) pacientes. El 79,9% fue de sexo femenino. El intervalo de edad predominante fue de 32 a 45 años. Se detectaron 43 reacciones adversas (0,02%); las más comunes fueron dolor abdominal (0,05%) y cefalea (0,03%). Conclusiones La población más interesada en el control ponderal en este estudio es la femenina (79,9%) y el grupo etario de 32 a 45 años. El profesional más consultado fue el nutriólogo. Solo se obtuvo el índice de masa corporal (29,2 kilogramos por metro cuadrado) de los sujetos que desarrollaron 43 reacciones adversas, las más comunes fueron dolor abdominal y cefalea.


Introduction Chronic diseases are on the rise and are associated with weight gain. Multidisciplinary strategies are required for its control. Methods The design was descriptive, observational and retrospective. The objectives of this communication were to describe the demographic and clinical characteristics and adverse reactions of overweight and obese people who were consumers of orlistat, attended by a call center during the period 2009 to 2017; and to identify the healthcare professional most consulted by them. The information was obtained from an existing database of a program of attention to people with overweight or obesity, interested in using orlistat (prospects) or users (patients). The study was carried out in Mexico and lasted seven years. The variables studied were demographic, clinical and adverse reactions. Results A total of 311,913 requests were collected from 126 607 subjects (104 711 prospects interested in consuming orlistat and 21 896 patients who already took it). The main activities were phone calls to the subject (35.9%). There were 104 711 requests: 82 810 (79.1%) prospects and 21 896 (20.9%) patients. 79.9% of all were female. The predominant age interval was 32 to 45 years. 43 adverse reactions (0.02%) were detected; the most common were abdominal pain (0.05%) and headache (0.03%). Conclusions The population most interested in weight control in this study was the female population (79.9%) and the age group from 32 to 45 years. The most consulted healthcare professional was the nutritionist. Only the body mass index (29.2 kilograms per square meter) of the subjects who developed 43 adverse reactions was obtained. There were 43 adverse reactions, the most common being abdominal pain and headache.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Anti-Obesity Agents/adverse effects , Overweight/drug therapy , Orlistat/adverse effects , Obesity/drug therapy , Abdominal Pain/chemically induced , Abdominal Pain/epidemiology , Retrospective Studies , Health Personnel/statistics & numerical data , Anti-Obesity Agents/administration & dosage , Call Centers/statistics & numerical data , Orlistat/administration & dosage , Headache/chemically induced , Headache/epidemiology , Mexico
10.
Article in English | LILACS | ID: biblio-880874

ABSTRACT

BACKGROUND: Vitamin D is a fat-soluble compound responsible for promoting intestinal absorption of calcium, and this, in turn, acts as a signal transmitter or activator as protein in secretory processes and release of hormones. VitaminD receptors are distributed in various tissues of the body and involved in biochemical reactions in the pathogenesis of several diseases, such as obesity. OBJECTIVE: The aim of this article is to provide updated information on the role of vitamin D in insulin resistance inobese individuals. METHODS: It was conducted a search of articles published in PubMED, SciELO, and LILACS database, without limit forthe year of publication, using the keywords"vitamin D","insulin resistance",and "obesity". RESULTS: Excess adipose tissue seems to impair insulin signaling by inhibiting the phosphorylation of its receptor, resultingin insulin resistance. Studies have evidenced role of vitamin D in mechanisms involved in the pathogenesis of insulin resistance in obesity by acting in improving glycemic control both by increasing hepatic and peripheral glucoseup take and by promoting the secretion of this hormone. CONCLUSIONS: Vitamin D exerts a protective effect in the treatment and prevention of insulin resistance in patients with obesity and protects the body against oxidative stress and chronic inflammation, contributing to glycemic control. Unfortunately, current data related to the effects of vitamin D supplementation on insulin resistance are still inconclusive


Subject(s)
Humans , Male , Female , Insulin Resistance/physiology , Obesity/drug therapy , Vitamin D/analysis , Vitamin D/therapeutic use
11.
Arch. endocrinol. metab. (Online) ; 61(4): 332-336, July-Aug. 2017. tab
Article in English | LILACS | ID: biblio-887575

ABSTRACT

ABSTRACT Objective The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. Subjects and methods This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. Results Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. Conclusion The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Bone and Bones/metabolism , Gastric Bypass/adverse effects , Biliopancreatic Diversion/adverse effects , Bone Remodeling/physiology , Obesity/surgery , Postoperative Period , Sodium/urine , Time Factors , Calcium/urine , Retrospective Studies , Alkaline Phosphatase/blood , Amino Acids/urine , Obesity/metabolism , Obesity/drug therapy
12.
Clinics ; 72(5): 317-324, May 2017. tab, graf
Article in English | LILACS | ID: biblio-840075

ABSTRACT

The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A systematic review of primary studies was conducted, followed by a direct meta-analysis (random effect) and mixed treatment comparison. Medline and other databases were searched. Heterogeneity was explored through I2 associated with a p-value. Of 739 identified publications, 25 were included in the meta-analysis. The global evaluation of Cochrane resulted in 19 studies with a high level of bias and six with unclear risk. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.


Subject(s)
Humans , Appetite Depressants/therapeutic use , Diethylpropion/therapeutic use , Mazindol/therapeutic use , Obesity/drug therapy , Overweight/drug therapy , Appetite Depressants/metabolism , Diethylpropion/metabolism , Mazindol/metabolism , Obesity/metabolism , Overweight/metabolism , Publication Bias , Reproducibility of Results , Risk Factors , Treatment Outcome , Weight Loss/drug effects
13.
An. acad. bras. ciênc ; 89(3,supl): 2155-2165, 2017. tab, graf
Article in English | LILACS | ID: biblio-886808

ABSTRACT

ABSTRACT Leaves of Psidium guajava L. (guava) have been widely used in the popular way for prevention and treatment of various diseases. Thus, the objective of this study was to evaluate the inhibitory potential of leaves aqueous extract from three cultivars of P. guajava (Pedro Sato, Paluma and Século XXI) on α-amylase, α-glycosidase, lipase, and trypsin enzymes, in the presence or not of simulated gastric fluid and to determine the content of phenolic compounds by high performance liquid chromatography. All cultivars presented the same composition in phenolic compounds, but in different proportions. The compounds identified are gallic acid, epigallocatechin gallate, syringic acid, o-coumaric acid, resveratrol, quercetin, and catechin (which was the major compound in all the cultivars evaluated). In the absence of simulated gastric fluid, it was observed different inhibitions exercised by the leaves aqueous extracts from three cultivars of P. guajava on each enzyme. In presence of simulated gastric fluid, all cultivars showed increase in the inhibition of lipase and α-glycosidase, and decrease in inhibition of α-amylase and trypsin enzymes. These results indicate that P. guajava leaves aqueous extracts from all cultivars evaluated possess potential of use as an adjuvant in the treatment of obesity and other dyslipidemias.


Subject(s)
Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Enzyme Inhibitors/pharmacology , Antioxidants/pharmacology , Obesity/drug therapy , Phenols/analysis , Water/analysis , Trypsin/pharmacology , Chromatography, High Pressure Liquid , Psidium/chemistry , alpha-Amylases/pharmacology , alpha-Glucosidases/pharmacology , Lipase/pharmacology
14.
Braz. j. med. biol. res ; 50(1): e5630, 2017. tab, graf
Article in English | LILACS | ID: biblio-839244

ABSTRACT

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.


Subject(s)
Animals , Male , Mice , Anti-Obesity Agents/pharmacology , Coumaric Acids/pharmacology , Cyclobutanes/pharmacology , Intra-Abdominal Fat/drug effects , Obesity/drug therapy , Adipose Tissue/pathology , Diet, High-Fat , Disease Models, Animal , Obesity/pathology
15.
Rev. cuba. farm ; 50(1)ene.-mar. 2016.
Article in Spanish | LILACS, CUMED | ID: biblio-844874

ABSTRACT

El sobrepeso y la obesidad son considerados un problema de salud pública a nivel mundial y a la postre, esa condición incentiva que millones de personas consuman productos para perder o controlar el peso. Dentro de este significativo mercado se puede encontrar una gran cantidad y variedad de productos que se comercializan con la denominación de origen natural. En la última década, se presenta que muchos de ellos son adulterados con sustancias sintéticas para potencializar su efecto. Una de las drogas sintéticas que se utiliza con ese propósito es la sibutramina, aun cuando fue retirada del mercado a nivel mundial en el año 2010 debido a sus graves efectos secundarios. En este trabajo se describen algunos ejemplos de casos importantes de adulteración de productos naturales en el orbe y las metodologías analíticas que se pueden utilizar en la determinación de su adulteración con sibutramina; luego de revisar y seleccionar artículos científicos de los últimos años y acceder a través de bases de datos Proquest, Scient Direct, Springer, EBSCO y otras del Sistema de Bibliotecas e Información de la Universidad de Costa Rica. Se encontró una variedad de técnicas y metodologías analíticas que permiten identificar y cuantificar la presencia de sibutramina en productos utilizados para bajar de peso(AU)


Overweight and obesity are considered as a public health problem worldwide and ultimately, this condition encourages millions of people to buy products for losing or controlling weight. In this significant market, it is possible to find a large number and great variety of products sold under the natural origin denomination. In the last decade, it has been found that many of them have been adulterated with synthetic substances to potentiate their effect. A synthetic drug that is used for this purpose is sibutramine, even though it was withdrawn from the worldwide market in 2010 because of its serious side effects. This paper described some significant examples of adulteration of natural products in the world and the analytical methodologies that can be used in determining the adulteration of these goods with sibutramine after reviewing and selecting scientific papers in recent years and access through databases Proquest, Scient Direct, Springer, EBSCO and others of the System of Libraries and Information at the University of Costa Rica. A range of techniques and analytical methods to identify and quantify sibutramine in slimming products was found(AU)


Subject(s)
Humans , Biological Products/therapeutic use , Overweight/epidemiology , Obesity/drug therapy , Chromatography, Thin Layer/methods , Costa Rica , Reference Drugs
16.
Rev. saúde pública (Online) ; 50: 25, 2016. tab, graf
Article in English | LILACS | ID: biblio-962204

ABSTRACT

ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.


RESUMO OBJETIVO Avaliar a evidência clínica de segurança e eficácia do Fenproporex para tratamento da obesidade. MÉTODOS Pesquisamos publicações em qualquer idioma nas bases Medline, Lilacs Cochrane Controlled Trials Register e também referências citadas por artigos e documentos relevantes. Dois autores avaliaram independentemente os estudos para inclusão e quanto ao risco de viés, dados coletados e precisão. Foram elegíveis estudos controlados com placebo que forneceram dados sobre a eficácia e segurança do Fenproporex para tratar a obesidade. RESULTADOS Apenas quatro estudos controlados preencheram critérios de inclusão. Um estudo placebo-controlado aleatorizado do Fenproporex foi encontrado nas bases eletrônicas. Três estudos controlados (em periódicos não indexados) foram identificados por buscas manuais. Pacientes com comorbidades (cardiovasculares ou outras) foram excluídos em todos os estudos. A duração dos estudos foi de 40 a 364 dias, com doses de 20 a 33,6 mg/d. Todos os estudos controlados encontraram maior perda de peso entre pacientes tratados com Fenproporex, comparados aos que receberam placebo, mas o efeito foi modesto. O Fenproporex causou reduções adicionais de peso de 4,7 kg (após um ano), 3,8 kg (após seis meses) e 1,55 kg (após dois meses), em média, em relação à dieta e exercício apenas (três ensaios). Insônia, irritabilidade e ansiedade foram os eventos colaterais mais frequentes nos quatro estudos. CONCLUSÕES Ensaios clínicos placebo-controlado aleatorizado do Fenproporex são escassos e os estudos controlados identificados apresentam importantes falhas metodológicas. Esses estudos sugerem que o Fenproporex é modestamente eficaz em promover perda de peso. Entretanto, eles não fornecem evidências de que o Fenproporex atenua a morbidade e mortalidade associada à obesidade. Esses estudos são insuficientes para avaliar o perfil risco-benefício do Fenproporex. Potencial de abuso e efeitos adversos do tipo anfetamínico são motivos de preocupação.


Subject(s)
Humans , Anti-Obesity Agents/adverse effects , Amphetamine/adverse effects , Amphetamines/adverse effects , Obesity/drug therapy , Placebos
17.
Braz. j. med. biol. res ; 47(9): 780-788, 09/2014. tab, graf
Article in English | LILACS | ID: lil-719321

ABSTRACT

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.


Subject(s)
Animals , Male , Adiposity/drug effects , Dyslipidemias/drug therapy , Ginkgo biloba/chemistry , Obesity/drug therapy , Phytotherapy , Blood Glucose/analysis , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diet, High-Fat/adverse effects , Dyslipidemias/metabolism , Eating/drug effects , Glucose Tolerance Test , Hypoglycemia/blood , Insulin Receptor Substrate Proteins/analysis , Insulin Resistance/physiology , Insulin/metabolism , Muscle, Skeletal/chemistry , Obesity/etiology , Plant Extracts/therapeutic use , Protein Tyrosine Phosphatase, Non-Receptor Type 1/analysis , Proto-Oncogene Proteins c-akt/analysis , Rats, Wistar , Signal Transduction/drug effects , Triglycerides/blood
18.
Ciênc. saúde coletiva ; 19(5): 1389-1400, 05/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-710535

ABSTRACT

Este estudo busca analisar os determinantes do consumo de inibidores de apetite (anfepramona, femproporex, mazindol e sibutramina) por meio da estimação de um modelo dinâmico de dados em painel para as capitais brasileiras e do Distrito Federal (DF) no período de 2009 a 2011. Os resultados revelam que o consumo de inibidores de apetite não acompanhou a distribuição geográfica dos indivíduos com excesso de peso e com obesidade nas unidades estudadas. Do consumo recorrente de inibidores, 79% são explicados pelo ocorrido no passado. Dentre as variáveis que explicam o consumo de inibidores, destacam-se os percentuais de adultos com obesidade e que dos que consomem frutas e hortaliças e a taxa de cobertura de planos de saúde. A análise farmacoeconométrica sugere que há problemas no uso racional dos inibidores de apetite nas capitais brasileiras e no DF, seja no que tange ao consumo desses medicamentos com outros fármacos - considerados ilegais pelo Conselho Federal de Medicina e pela Anvisa - e, também, na indicação terapêutica de uso desses produtos.


The scope of this study is to analyze the determinants of the use of appetite suppressants (amfepramone, femproporex, mazindol and sibutramine) through the estimation of a dynamic panel dataset model for the Brazilian state capitals and the Federal District (DF) in the period from 2009 to 2011. The results show that consumption of appetite suppressants did not follow the geographic distribution of overweight and obese individuals across the capitals and DF. There is a recurrent consumption of appetite inhibitors, in which 79% of the current consumption of these drugs is explained by past consumption. Among the variables that explain the use of inhibitors, the percentage of obese adults, the percentage of adults who habitually consume fruit and vegetables, and the coverage rate of health plans stand out. The pharmaco-econometric analysis suggests that there are problems in the rational use of appetite suppressants in the Brazilian state capitals and the Federal District with respect to both the combined consumption of these drugs with other medicines - deemed illegal by the Federal Council of Medicine and ANVISA - and in the therapeutic prescription of these products.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Appetite Depressants/economics , Drug Utilization/economics , Drug Utilization/standards , Obesity/economics , Appetite Depressants/therapeutic use , Brazil , Models, Econometric , Obesity/drug therapy
19.
Article in English | WPRIM | ID: wpr-39643

ABSTRACT

The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology.


Subject(s)
Animals , Diabetes Mellitus, Type 2/drug therapy , GTP-Binding Protein alpha Subunits/genetics , Humans , Insulin-Secreting Cells/metabolism , Obesity/drug therapy , Receptor, Melatonin, MT2/genetics , Receptors, Adrenergic, alpha-1/genetics , Receptors, Prostaglandin/genetics
20.
Rio de Janeiro; s.n; 2014. 99 p.
Thesis in Portuguese | LILACS | ID: lil-750225

ABSTRACT

As associações entre obesidade, doença hepática gordurosa não alcoólica (NAFLD) e diabetes mellitus tipo 2 (DM2) são bem estabelecidas, e o sistema renina-angiotensina (SRA) pode proporcionar uma ligação entre eles. O bloqueio do SRA em diferentes níveis pode estar relacionado a respostas na resistência à insulina, remodelagem do pâncreas e do fígado em um modelo de obesidade induzida por dieta. Camundongos C57BL/6 foram alimentados com uma dieta hiperlipídica (HF) durante oito semanas e depois tratados com alisquireno (50 mg/kg/dia), enalapril (30 mg/kg/dia) ou losartana (10 mg/kg/dia) por um período adicional de seis semanas. As drogas foram incorporadas na dieta. Avaliou-se a massa corporal (MC), pressão arterial, consumo e gasto energético (GE), metabolismo da glicose e lipídico, histopatologia pancreática e hepática, análise hormonal, imunohistoquímica, perfil gênico e/ou proteico do SRA no pâncreas, gliconeogênese hepática, sinalização da insulina, oxidação e acúmulo lipídico. Todos os inibidores do SRA reduziram significativamente o aumento da pressão arterial nos camundongos alimentados com dieta HF. O tratamento com enalapril, mas não alisquireno ou losartana, reduziu o ganho de MC e a ingestão alimentar; aumentou o GE; amenizou a intolerância à glicose e resistência à insulina; melhorou a massa de células alfa e beta; impediu a redução da adiponectina plasmática e restaurou a sensibilidade à leptina. Além disso, o tratamento com enalapril melhorou a expressão proteica nas ilhotas pancreáticas de Pdx1, GLUT2, ECA2 e do receptor Mas. O tratamento com losartana apresentou uma elevação na expressão proteica de AT2R no pâncreas...


The associations between obesity, NAFLD (non-alcoholic fatty liver disease) and diabetes are well established, and the renin–angiotensin system (RAS) may provide a link among them. . The blocking of the RAS at different levels may be related to responses on insulin resistance, remodeling of the pancreas and liver in a model of diet-induced obesity. Mice (C57BL/6) were fed on a high-fat (HF) diet for 8 weeks and then treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for an additional 6 weeks. The drugs were incorporated into the diet. We assessed body mass (BM), blood pressure, energy intake and expenditure (EE), glucose and lipid metabolism, pancreatic and hepatic histopathology, hormonal analysis, immunohistochemistry, the expression profile of genes and/or proteins affecting pancreas RAS, hepatic gluconeogenesis, insulin signaling and lipid oxidation and accumulation. All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated BM gain, increased EE, enhanced the glucose intolerance and insulin resistance; improved the alpha and beta cell mass; prevented the reduction of plasma adiponectin and restored leptin sensibility. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression in the pancreas. In the liver, the enalapril administration improved hepatic steatosis, triglycerides and prevented the increase hepatic protein levels of PEPCK, G6Pase and GLUT2...


Subject(s)
Animals , Mice , Diet, High-Fat , Enalapril/therapeutic use , Obesity/diet therapy , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors , /drug therapy , Fatty Liver/metabolism , Hypertension/drug therapy , Islets of Langerhans/metabolism , Obesity/complications , Obesity/drug therapy , Pancreas/metabolism , Insulin Resistance/immunology
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