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1.
Einstein (Sao Paulo) ; 18: eAO4876, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576909

RESUMO

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.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Sericinas/uso terapêutico , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/análise , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Fígado Gorduroso/patologia , Trânsito Gastrointestinal/efeitos dos fármacos , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/fisiopatologia , Reprodutibilidade dos Testes , Sericinas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/análise , Ganho de Peso/efeitos dos fármacos
3.
Life Sci ; 237: 116914, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622606

RESUMO

AIMS: The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses. MAIN METHODS: Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1-α mRNA expression in the brown adipose tissue were assessed. KEY FINDINGS: Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue. SIGNIFICANCE: Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Biologia Computacional/métodos , Dieta Hiperlipídica/efeitos adversos , Ácido Gálico/farmacologia , Metaboloma/efeitos dos fármacos , Obesidade/metabolismo , Sirtuína 1/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Sirtuína 1/genética , Termogênese/efeitos dos fármacos
4.
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
5.
Biomed Environ Sci ; 32(8): 578-591, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31488234

RESUMO

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION: These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/metabolismo , Lactobacillus plantarum/química , Obesidade/tratamento farmacológico , Probióticos/metabolismo , Proteína Desacopladora 1/metabolismo , Células 3T3 , Adipócitos/fisiologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/fisiologia , Ração Animal/análise , Animais , Fármacos Antiobesidade/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Dieta , Fermentação , Hordeum/química , Masculino , Camundongos , Obesidade/genética , Extratos Vegetais/química , Probióticos/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteína Desacopladora 1/genética
6.
Medicine (Baltimore) ; 98(37): e17058, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517826

RESUMO

RATIONALE: The prevalence of obesity has increased over the past few years, becoming a public health problem. Generally, the primary therapeutic remedies are diet, physical exercise, medication, and bariatric surgery. However, an increased number of obese and overweight people are using complementary and herbal slimming supplements. PATIENT CONCERNS: A 70-years-old Caucasian woman presented to the outpatient clinic with tachycardia (>100 bpm), insomnia, anxiety, and recent weight loss (6 kilos in 3 months). She had no previous thyroid disease, but she presented transient hyperthyroidism at 3 months after ingestion of tablets containing kelp seaweeds. DIAGNOSES: Hypertensive and obese patient, without previous thyroid disease, presented with transient hyperthyroidism at 3 months following ingestion of tablets containing kelp seaweed. INTERVENTIONS: The kelp-containing tablets were discontinued, and antithyroid therapy with Methimazole was initiated as follows: Methimazole at 15 mg/day for 1 month, at 10 mg/day in the second month, and 5 mg/day for the third month. OUTCOMES: After 3 months of antithyroid therapy and without the consumption of kelp - containing tablets, normal thyroid function was regained. Further analysis revealed normal thyroid function, so the hyperthyroidism reversed completely. LESSONS: Adults who consume complementary medication based on kelp seaweed should be informed of the risk of developing thyroid dysfunction also in the absence of any pre-existing thyroid disease. Due to the high iodine content, supplements containing kelp should be taken with the supervision of a physician and with monitoring of thyroid function.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Terapias Complementares/efeitos adversos , Hipertireoidismo/etiologia , Kelp , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico
7.
Adv Gerontol ; 32(3): 431-438, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512431

RESUMO

In recent years, the effectiveness of high-dose metformin (MF) to treat the endocrine and oncological diseases has been shown. However, the use of high-dose MF may be associated with the lactic acidosis and the liver dysfunctions. The aim of the work was to study the effect of long-term (10 days) oral administration of a relatively high dose of MF (600 mg/kg per day) into yellow C57Bl/6J (Ay/a) Agouti line mice with the melanocortin type obesity on the liver function, which was evaluated by the morphology of hepatocytes and the severity of steatosis, the expression of the inflammatory and apoptotic factors of and the activity of aminotransferases, as well as on the plasma lactate level in the animals. In Agouti line mice, MF (600 mg/kg per day) caused a decrease in the body and fat weight, led to the reduced hyperglycemia, hyperinsulinemia and hyperleptinemia, and restored the sensitivity to glucose and insulin. At the same time, in the liver of Agouti line mice treated with MF, the small-drop and large-drop fatty degeneration and the hydropic degeneration were attenuated, and the expression of pro-inflammatory IL-1ß and pro-apoptotic Bax protein and the Bax/Bcl-2 ratio did not differ from the control C57Bl/6J (a/a) mice. In the blood of Agouti line mice treated with MF, the activity of alanine aminotransferase was normalized, and the lactate levels was increased, but to a moderate degree. It was concluded that the high-dose MF did not induce the lactic acidosis in Agouti line mice, and at the same time it restored the liver functions impaired in the melanocortin obesity. This allows us to consider the use of the high doses of MF as one of the possible ways to treat obesity and metabolic disorders that are associated with the hepatic steatosis.


Assuntos
Fígado , Melanocortinas , Metformina , Obesidade , Animais , Dasyproctidae , Fígado/efeitos dos fármacos , Melanocortinas/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/fisiopatologia
8.
J Agric Food Chem ; 67(38): 10595-10603, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31475817

RESUMO

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , beta-Criptoxantina/administração & dosagem , Obesidade/tratamento farmacológico , Receptores do Ácido Retinoico/metabolismo , Proteína Desacopladora 1/genética , Animais , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Receptores do Ácido Retinoico/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
9.
Eur J Med Chem ; 181: 111565, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31387062

RESUMO

The human Carbonic anhydrases (hCA) VA and VB play a key role in ureagenesis, gluconeogenesis, lipogenesis and in the metabolism regulation, thus representing highly popular drug targets. Albeit several hCA inhibitors have been designed and are currently in clinical use, serious drug interactions have been reported due to their poor selectivity. In this perspective, the drug repurposing approach could be a useful tool in order to investigate the drug promiscuity/polypharmacology profile. In this study, virtual screening techniques and in vitro assays were combined to identify novel selective hCA VA inhibitors from among around 94000 compounds. The docking analysis highlighted 12 promising best hits, biologically characterized in terms of their hCA VA inhibitory activity. Interestingly, among them, the anticancer agents fludarabine and lenvatinib and the antiepileptic rufinamide were able to selectively inhibit the enzyme activity in the micromolar range, while a pyrido-indole derivative, the homovanillic acid sulfate and the desacetyl metabolite of the antibacterial cephapirin in the nanomolar range.


Assuntos
Fármacos Antiobesidade/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Reposicionamento de Medicamentos , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/química , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Projeto Auxiliado por Computador , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular , Obesidade/metabolismo
10.
Life Sci ; 234: 116780, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430453

RESUMO

Bronchial asthma and obesity are common health problems. Obesity is already responsible for 300,000 deaths per year. AIMS: The aim of the present study was to assess whether apocynin, alpha lipoic acid and probiotic administration in combination with low-fat diet supplementation influences the levels of antioxidant enzymes in the pulmonary tissues of obese asthmatic mice. MAIN METHODS: The study was performed on male C57/BL6 mice divided into 10 groups: (I) control; (II) asthma; (III) obesity; (IV) asthma + obesity; (V) asthma + obesity + apocynin p.o. 15 mg/kg/day for 12 weeks; (VI) asthma + obesity + low-fat diet for 12 weeks; (VII) asthma + obesity + low-fat diet for 12 weeks with apocynin p.o. 15 mg/kg/day; (VIII) asthma + obesity + low-fat diet with probiotics for 12 weeks; (IX) asthma + obesity + low-fat diet for 12 weeks with lipoic acid p.o. 100 mg/kg/day for 12 weeks; (X) asthma + obesity + standard diet with probiotics for 12 weeks. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity were examined. The administration of apocynin alone and apocynin in combination with a low-fat diet resulted in a significant increase in SOD values (respectively p < 0.001; p = 0.010). Application of probiotics resulted in a decrease in CAT activity (p = 0.037) and an increase in GPx activity (p < 0.001) compared to obese asthmatic mice. The administration of lipoic acid resulted in an increase in GR activity (p = 0.024 vs. control). KEY FINDINGS: Supplementation containing apocynin, lipoic acid and probiotics has a positive influence on the antioxidant capacity of the pulmonary tissues of obese asthmatic mice. SIGNIFICANCE: These results may contribute to the development of new therapeutic approaches.


Assuntos
Acetofenonas/uso terapêutico , Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Obesidade/tratamento farmacológico , Probióticos/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Asma/complicações , Asma/metabolismo , Catalase/análise , Catalase/metabolismo , Glutationa Peroxidase/análise , Glutationa Peroxidase/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo
11.
Eur J Med Chem ; 182: 111593, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446245

RESUMO

A novel series of phenylthiazoles bearing cyclic amines at the phenyl-4 position was prepared with the objective of decreasing lipophilicity and improving the overall physicochemical properties and pharmacokinetic profile of the compounds. Briefly, the piperidine ring (compounds 10 and 12) provided the best ring size in terms of antibacterial activity when tested against 16 multidrug-resistant clinical isolates. Both compounds were superior to vancomycin in the ability to eliminate methicillin-resistant Staphylococcus aureus (MRSA), residing within infected macrophages and to disrupt mature MRSA biofilm. Additionally, compounds 10 and 12 exhibited a fast-bactericidal mode of action in vitro. Furthermore, the new derivatives were 160-times more soluble in water than the previous lead compound 1b. Consequently, compound 10 was orally bioavailable with a highly-acceptable pharmacokinetic profile in vivo that exhibited a half-life of 4 h and achieved a maximum plasma concentration that exceeded the minimum inhibitory concentration (MIC) values against all tested bacterial isolates.


Assuntos
Aminas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Obesidade/tratamento farmacológico , Tiazóis/farmacologia , Aminas/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Obesidade/microbiologia , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/metabolismo , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química
12.
J Agric Food Chem ; 67(36): 10107-10115, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31434473

RESUMO

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of Carapa guianensis, Meliaceae, known as andiroba in high-fat-diet (HFD)-fed mice. C57BL/6 mice were fed a low-fat diet or an HFD and orally administered CG-1 (20 mg/kg) for 7 weeks. CG-1 lowered the body weight gain and improved the serum triglyceride level and insulin sensitivity in HFD-fed mice. The expression level of the adipogenesis-related genes was lowered by CG-1 in the visceral white adipose tissue (vWAT). The mRNA expression level of the macrophage-related genes decreased in vWAT following the administration of CG-1 to HFD-fed mice. It is noteworthy that CG-1 activated the brown adipose tissue (BAT) with enhanced expression of uncoupling protein 1 and increased the rectal temperature in HFD-fed mice. These results indicate that the limonoid CG-1 decreased body weight gain and ameliorated hypertriglyceridemia and insulin resistance with the activation of BAT in HFD-fed mice.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/administração & dosagem , Resistência à Insulina , Limoninas/administração & dosagem , Meliaceae/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Sementes/química , Triglicerídeos/sangue , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Ganho de Peso/efeitos dos fármacos
13.
Internist (Berl) ; 60(9): 895-902, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31346639

RESUMO

BACKGROUND: The worldwide rise in overweight and obesity is paralleled by an increasing prevalence of type-2 diabetes. Apart from bariatric surgery, treatment options to decrease body weight are often underwhelming. Innovative pharmacological options are required to cope with the global "diabesity" pandemic. OBJECTIVES: Particular novel pharmacological approaches are discussed, with a special focus on polyagonist-based pharmacotherapies. MATERIALS AND METHODS: Articles on co- and tri-agonists for the treatment of obesity and diabetes are presented and discussed. RESULTS: Unimolecular peptides have been developed for the treatment of obesity and type-2 diabetes. These peptides activate the receptors of multiple hormones and bundle their positive effects in one single molecule. In preclinical studies, polyagonists targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon, or glucose-dependent insulinotropic peptide (GIP) were promising to reduce body weight and blood glucose. GLP-1-mediated delivery of the nuclear hormones estrogen or dexamethasone also yielded beneficial effects in preclinical studies of obesity. CONCLUSIONS: Polyagonists represent an innovative strategy for the development of novel pharmacotherapies to treat obesity and diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Incretinas/uso terapêutico , Obesidade/tratamento farmacológico , Polifarmacologia , Polipeptídeo Inibidor Gástrico , Peptídeo 1 Semelhante ao Glucagon , Humanos , Insulina
14.
Plant Foods Hum Nutr ; 74(3): 277-286, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278560

RESUMO

Obesity is a major worldwide health threat. It is characterized by an abnormal adipose tissue overgrowth together with increased monocytes infiltration, causing inflammation and oxidative stress, events associated with several illnesses. Investigations have focused on the benefits of native fruit consumption, claiming these to be natural sources of bioactive compounds with antioxidant and anti-inflammatory characteristics. It has been widely stated that berries are a source of the most antioxidant compounds, and, thus, seem highly promising to endure research efforts on these vegetal matrices. The present article describes botanical, chemical and biomedical features of the Chilean native berries, Aristotelia chilensis, Ugni molinae, and Berberis microphylla. This work aims to potentiate incoming research focused on the search for novel treatments for first-order diseases with these particular plant sources.


Assuntos
Berberis/química , Elaeocarpaceae/química , Frutas/química , Myrtaceae/química , Obesidade/tratamento farmacológico , Compostos Fitoquímicos/análise , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Antioxidantes/análise , Antioxidantes/farmacologia , Chile , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Obesidade/complicações , Estresse Oxidativo , Compostos Fitoquímicos/farmacologia
15.
Curr Top Med Chem ; 19(16): 1418-1435, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31284863

RESUMO

The Cannabinoid CB1 Receptor (CB1R) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the CB1R in the last two decades.


Assuntos
Antipsicóticos/efeitos adversos , Antagonistas de Receptores de Canabinoides/efeitos adversos , Obesidade/tratamento farmacológico , Receptor CB1 de Canabinoide/antagonistas & inibidores , Abandono do Hábito de Fumar , Animais , Antipsicóticos/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Humanos , Obesidade/metabolismo , Receptor CB1 de Canabinoide/metabolismo
16.
J Agric Food Chem ; 67(25): 7136-7146, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240929

RESUMO

Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) are organosulfur phytochemicals rich in cruciferous vegetables. We investigated the antiobesity and antihepatosteatosis activities of BITC and PEITC and the working mechanisms involved. C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.5 (L) or 1 g/kg (H) BITC or PEITC for 18 weeks. Compared with the HFD group, BITC or PEITC decreased the final body weight of mice in a dose-dependent manner [39.0 ± 3.1 (HFD), 34.4 ± 3.2 (BITC-L), 32.4 ± 2.8 (BITC-H), 36.2 ± 4.4 (PEITC-L), and 32.8 ± 2.9 (PEITC-H) g, p < 0.05], relative weight of epididymal fat [5.7 ± 0.4 (HFD), 4.7 ± 0.7 (BITC-L), 3.7 ± 0.3 (BITC-H), 4.4 ± 1.0 (PEITC-L), and 3.2 ± 0.6 (PEITC-H) %, p < 0.05], hepatic triglycerides [98.4 ± 6.0 (HFD), 81.0 ± 8.9 (BITC-L), 63.5 ± 5.6 (BITC-H), 69.3 ± 5.6 (PEITC-L), and 49.4 ± 2.9 (PEITC-H) mg/g, p < 0.05], and plasma total cholesterol [140 ± 21.3 (HFD), 109 ± 5.6 (BITC-L), 101 ± 11.3 (BITC-H), 126 ± 8.3 (PEITC-L), and 91.8 ± 12.7 (PEITC-H) mg/dL, p < 0.05]. Q-PCR and immunoblotting assays revealed that BITC and PEITC suppressed the expression of liver X receptor α, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, fatty acid synthase, and acetyl-CoA carboxylase in both epididymal adipose and liver tissues. After a single oral administration of 85 mg/kg BITC or PEITC, the maximum plasma concentrations ( Cmax) of BITC and PEITC were 5.8 ± 2.0 µg/mL and 4.3 ± 1.9 µg/mL, respectively. In 3T3-L1 adipocytes, BITC and PEITC dose-dependently reduced adipocyte differentiation and cell cycle was arrested in G0/G1 phase. These findings indicate that BITC and PEITC ameliorate HFD-induced obesity and fatty liver by down-regulating adipocyte differentiation and the expression of lipogenic transcription factors and enzymes.


Assuntos
Adipogenia/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Isotiocianatos/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/fisiopatologia
17.
Endocr Pract ; 25(10): 1022-1028, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31241358

RESUMO

Objective: The effectiveness of anti-obesity medications (AOMs) outside of clinical trials is unclear. The objective of this study was to compare the short-term effectiveness of AOMs in real-world practice. Methods: This retrospective study included adults aged ≥18 years, with body mass index ≥30 kg/m2 or ≥27 kg/m2 with at least one obesity-related comorbidity who were prescribed phentermine hydrochloride, phenterminetopiramate, bupropion-naltrexone, or lorcaserin for 12 consecutive weeks between 2006 and 2016 at a large tertiary healthcare system. Propensity score-matched cohorts were created for each pair of AOMs. The primary outcomes were percent and absolute weight loss from baseline after 12 weeks. A prediction model was constructed to estimate weight loss with different AOMs based on demographic and clinical data. Results: Of the 3,411 patients included in this study, patients lost an average of 3.45% of body weight from baseline. All AOMs were associated with a significant weight loss from baseline (P<.0001). Patients lost the highest percentage of body weight on phentermine hydrochloride (3.75 ± 5.66%), followed by phentermine-topiramate (3.63 ± 5.7%), bupropion-naltrexone (2.66 ± 5.03%), and lorcaserin (1.84 ± 6.69%). In propensity-matched cohorts, patients taking phentermine hydrochloride lost more weight than those taking lorcaserin or bupropion-naltrexone, and patients taking phentermine topiramate lost more weight than patients taking lorcaserin. Conclusion: In real-world practice, AOMs are associated with clinically meaningful weight loss of 2 to 4% after 12 weeks. In this study, phentermine hydrochloride and phentermine topiramate produced the most weight loss. AOMs should be seriously considered as part of the armamentarium to treat patients with obesity. Abbreviations: AOM = anti-obesity medication; BMI = body mass index; EMR = electronic medical record; FDA = Food and Drug Administration; T2D = type 2 diabetes.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2 , Perda de Peso , Adulto , Frutose , Humanos , Obesidade/tratamento farmacológico , Estudos Retrospectivos , Topiramato
18.
Artigo em Chinês | MEDLINE | ID: mdl-31245957

RESUMO

OBJECTIVE: To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning. METHODS: The male C57BL/6J mice were divided into three groups: normal control group, genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days, normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region, inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1 (UCP1) was determined by real-time PCR and Western blot respectively. RESULTS: The wet weight of white fat in genipin-treated mice was decreased by 16% , and 28% in that of cold-stimulus mice, compared with the normal control group (P<0.05).After treatments of genipin and cold-stimulus, the color of white adipose tissues was darker, and the size of lipid droplets in adipocytes was smaller, whereas the number was increased.Compared with the normal control group, UCP1 expression was increased obviously in fat tissues, including the subcutaneous and visceral white adipose tissues, and brown adipose tissue after treated with genipin and cold-stimulus (P<0.05). CONCLUSION: Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression, which could contribute to the loss of body weight against obesity.


Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco , Colagogos e Coleréticos , Iridoides , Proteína Desacopladora 1 , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Colagogos e Coleréticos/farmacologia , Iridoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Proteína Desacopladora 1/efeitos dos fármacos , Regulação para Cima
19.
Phytother Res ; 33(8): 2015-2022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31206225

RESUMO

INTRODUCTION: It is well known that there is a strong linkage between obesity, systemic low-grade inflammation, and oxidative stress in the pediatric population. Possible strategies that might control obesity and its relevant problems in this crucial group are of utmost importance. Therefore, the aim of this study was to evaluate the effects of curcumin supplements on inflammation, oxidative stress, and chemerin levels in adolescent girls. METHODS: Totally, 60 overweight and obese adolescent girls were randomly assigned to either placebo or intervention group in a randomized placebo-controlled parallel trial design. Adolescents consumed one 500-mg curcumin or placebo per day along with a slight weight loss diet for 10 weeks. High-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC), malondialdehyde (MDA), chemerin levels, and anthropometric measurements were assessed at the beginning and end of the trial. RESULTS: Curcumin supplementation had a significant effect on IL-6 levels and oxidative stress markers including TAC and MDA in crude model. After controlling the effects of confounders, curcumin supplementation had a substantial effect on inflammation (hs-CRP and IL-6) and oxidative stress (TAC) marker of adolescents. DISCUSSION: Ten weeks of curcumin supplementation had beneficial effects on inflammation and oxidative stress markers among postpubescent overweight and obese girl adolescents.


Assuntos
Curcumina/uso terapêutico , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Adolescente , Curcumina/farmacologia , Feminino , Humanos
20.
J Agric Food Chem ; 67(25): 7040-7049, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199141

RESUMO

Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first induced to develop obesity by being fed a high-fat diet. The obese rats were then fed a control diet, AIN-93M (group HFD), or a 10% FP diet (group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, and serous proteins within the leptin-neuropeptide Y (NPY) and AMP-activated protein kinase (AMPK) signaling pathway were determined and analyzed. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15% ± 0.30% in group HFD to 478 ± 10 g and 1.38% ± 0.48% in group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Linho/química , Leptina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Saciação/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Obesidade/metabolismo , Obesidade/psicologia , Extratos Vegetais/química , Polissacarídeos/química , Ratos , Ratos Wistar , Sementes/química , Transdução de Sinais/efeitos dos fármacos
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