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1.
Wiad Lek ; 73(1): 63-67, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32124808

RESUMEN

OBJECTIVE: The aim: To study the dynamics of markers of angiogenesis based on insulin-like growth factor-1 (IGF-1) and endostatin, as well as to determine 6-month survival in patients taking zofenopril from the first day of AMI with and without obesity. PATIENTS AND METHODS: Materials and methods: using enzyme immunoassay, we determined the level of endostatin and IGF-1 in serum on days 1 and 12 in patients with AMI with the presence and absence of obesity, and a statistical processing of the data obtained. RESULTS: Results: The relationship between obesity and angiogenesis indicators, both activators and inhibitors, was determined, and a significant relationship was found between zofenopril therapy and angiogenesis activator IGF-1. Differences in the survival of patients with complicated AMI were determined depending on the choice of ACE inhibitor in favor of a higher survival rate of patients who took zofenopril. CONCLUSION: Conclusions: patients who underwent complicated AMI, taking zofenopril, have a higher survival rate during the 6-month follow-up period. Zofenopril stimulated angiogenesis in the examined patients, which was expressed in patients with and without obesity.


Asunto(s)
Captopril/análogos & derivados , Endostatinas/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Infarto del Miocardio , Obesidad/tratamiento farmacológico , Captopril/uso terapéutico , Humanos , Infarto del Miocardio/tratamiento farmacológico
2.
Biochem Soc Trans ; 48(1): 291-300, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-32049315

RESUMEN

Modulating the activity of the Src Homology 2 (SH2) - containing Inositol 5'-Phosphatase (SHIP) enzyme family with small molecule inhibitors provides a useful and unconventional method of influencing cell signaling in the PI3K pathway. The development of small molecules that selectively target one of the SHIP paralogs (SHIP1 or SHIP2) as well as inhibitors that simultaneously target both enzymes have provided promising data linking the phosphatase activity of the SHIP enzymes to disorders and disease states that are in dire need of new therapeutic targets. These include cancer, immunotherapy, diabetes, obesity, and Alzheimer's disease. In this mini-review, we will provide a brief overview of research in these areas that support targeting SHIP1, SHIP2 or both enzymes for therapeutic purposes.


Asunto(s)
Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Descubrimiento de Drogas , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/química , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo
3.
Life Sci ; 247: 117414, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32035928

RESUMEN

AIMS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to significantly reduce body weight. This study investigated whether SGLT2 inhibitors directly affect adipose tissues and the underlying mechanisms in vivo and in vitro. MAIN METHODS: Male C57BL/6 mice were fed a normal diet, high-fat diet (HFD), or HFD with canagliflozin for 14 weeks. 3T3-L1 adipocytes were treated with canagliflozin. Metabolic parameters were measured. KEY FINDINGS: Canagliflozin reduced body weight, fat mass, and white adipose tissue (WAT) weight and inhibited adipocyte hypertrophy. Canagliflozin improved glucose and lipid metabolic disorders induced by HFD. Furthermore, canagliflozin treatment reversed the suppressed mRNA and protein expression of PGC-1α, NRF1, tfam and CPT1b, which are markers of mitochondrial biogenesis, function and fatty acid oxidation in mice with obesity. In vitro, canagliflozin increased mitochondrial DNA to nuclear DNA and upregulated the expression of PGC-1α, NRF1, tfam, COX5b, COX8b, Atp5o, and CPT1b mRNA and PGC-1α, NRF1, tfam, COX5b, CPT1b protein in 3T3-L1 adipocytes in a dose-dependent manner, while these increases were inhibited by GW6471, a PPARα antagonist. SIGNIFICANCE: Our study showed that canagliflozin protected against HFD-induced obesity and obesity-related metabolic disorders by improving mitochondrial function and fatty acid oxidation in adipose tissue and adipocytes. Such energy-dissipating effects of canagliflozin may be mediated by PPARα.


Asunto(s)
Canagliflozina/uso terapéutico , Ácidos Grasos/metabolismo , Mitocondrias/metabolismo , Obesidad/tratamiento farmacológico , PPAR alfa/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Células 3T3-L1 , Adipocitos/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Canagliflozina/farmacología , Dieta Alta en Grasa , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , PPAR alfa/genética , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología
4.
Medicine (Baltimore) ; 99(5): e18955, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000419

RESUMEN

BACKGROUND: Obesity is associated with metabolic syndrome, a condition that increases one's risk for heart disease and other conditions. The prevalence of obesity and associated diseases have steadily increased among Korean adults. The effect of the herbal medicines Daesiho-tang (DSHT) and Chowiseungcheng-tang (CST) on obesity have been reported. The purpose of this study is to evaluate the efficacy and safety of Daesiho-tang and Chowiseungcheng-tang on obese Korean women with high risk for metabolic syndrome. METHODS/DESIGN: This study is a randomized, double-blinded, placebo-controlled, multi-center, 3-arm, parallel group clinical trial. A total of 120 participants will be enrolled and randomly assigned to the Daesiho-tang group, the Chowiseungcheng-tang group, or the placebo group in a 1:1:1 ratio using an internet-based randomization system at visit 2. Each group will be administered DSHT, CST, or placebo 3 times per day for 12 weeks. The primary outcome is to evaluate the changes in mean body weight of participants in the DSHT and CST groups and compare with those in the placebo group, and determine their statistical significance, if any, after 12 weeks. The secondary outcomes are the following: changes in body fat percentage and body fat mass, changes in waist circumference, waist-to-hip ratio, and body mass index, changes in serum lipids, fasting blood sugar, blood pressure, and C-reactive proteins (CRP) levels between visit 1 and visit 5 measurements. Changes in visceral fat volume determined through abdominal computed tomography, patient-reported health outcomes surveys-the Korean version of the Obesity-related Quality of Life and the Korean version of Eating Attitudes Test. DISCUSSION: This study will provide research methodologies for evaluating the efficacy and safety of Daesiho-tang and Chowiseungcheng-tang on obese Korean women with high risk for metabolic syndrome. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02651454. Registered on 11 January 2016.Protocol version: The final approved version of the trial protocol is V1.3.(2017.11.10).


Asunto(s)
Medicina Tradicional Coreana , Síndrome Metabólico/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Obesidad/tratamiento farmacológico , Fitoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Adolescente , Adulto , Anciano , Fármacos Antiobesidad/uso terapéutico , Femenino , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/epidemiología , Selección de Paciente , Proyectos Piloto , República de Corea , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
5.
Diabetes Res Clin Pract ; 160: 108025, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31954752

RESUMEN

Metformin represents a striking example of a "historical nemesis" of a drug. About 40 years after its marketing in Europe, once demonstrated its efficacy and safety, metformin was registered also in the U.S. A few years later, it has become a mainstay in T2DM treatment, according to all international Scientific Societies guidelines. Today, despite the advent of new innovative drugs, metformin still persists as a first-choice drug in T2DM. This success is largely justified. In fact, over the years, also positive effects on health increased. In particular, evidence has been accumulated on a beneficial impact against many other aging-related morbidities (obesity, metabolic syndrome, cardiovascular disease, cancer, cognitive decline and mortality). This literature review describes preclinical and clinical evidence favoring the "anti-aging" therapeutic potential of metformin outside of T2DM. The rationale to the use of metformin as part of a combined therapy in a variety of clinical settings, allowing for a reduction of the chemotherapy dose in cancer patients, has also been discussed. In particular, the focus was on metformin action on RAS/RAF/MAPK pathway. In the end, the real challenge for metformin could be to fully demonstrate beneficial effects on health even in non-diabetic subjects.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Neoplasias/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Humanos , Hipoglucemiantes/farmacología , Masculino , Metformina/farmacología , Morbilidad
6.
PLoS One ; 15(1): e0227637, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31929574

RESUMEN

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Fármacos Antiobesidad/farmacología , Hesperidina/farmacología , Inflamación/tratamiento farmacológico , Resistencia a la Insulina , Obesidad/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/química , Fármacos Antiobesidad/química , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Quimioterapia Combinada , Hesperidina/química , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Inflamación/metabolismo , Inflamación/patología , Leptina/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Obesidad/metabolismo , Obesidad/patología , Orlistat/química , Orlistat/farmacología , Ratas Wistar
7.
Am J Clin Nutr ; 111(4): 757-768, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31950134

RESUMEN

BACKGROUND: Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. OBJECTIVES: The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. METHODS: We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. RESULTS: Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group. CONCLUSIONS: Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.


Asunto(s)
Colecalciferol/administración & dosificación , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Adipoquinas/metabolismo , Adolescente , Glucemia , Presión Sanguínea , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatología , Niño , Suplementos Dietéticos/análisis , Femenino , Corazón/fisiopatología , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Masculino , Obesidad/genética , Obesidad/metabolismo , Obesidad/fisiopatología , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/fisiopatología , Rigidez Vascular
8.
J Agric Food Chem ; 68(3): 779-787, 2020 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-31894986

RESUMEN

The chain length of fructan determines its different physiological effects. This study is to explore the effects of low-performance inulin [LPI, degree of polymerization (DP) ≤ 9] and high-performance inulin (HPI, DP ≥ 23) on obesity-associated liver injury of high-fat diet (HFD) feeding mice and its underlying mechanism. Eight weeks of supplementation of C57BL/6J mice with HPI, relative to LPI (p < 0.05), caused the more efficient improvement against the HFD-induced liver insulin resistance through activating IRS1/PI3K/Akt pathway and reduced protein expressions of inflammatory factors nuclear factor-kappaB (NF-κB) and interleukin-6 (IL-6) in the liver. HPI exhibited the more positive effects on liver steatosis by inhibiting acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and sterol regulatory element binding protein 1 (SREBP1) in comparison with LPI (p < 0.05). HPI also increased acetic acid, propionic acid, and butyric acid levels in the colon of HFD-fed mice (p < 0.05). Compared to LPI, HPI feeding of HFD-fed mice led to the more effective decrease in the Firmicutes abundance from 72.1% to 34.5%, but a more significant increase in the Bacteroidetes population from 19.8 to 57.1% at the phyla level, and increased the abundance of Barnesiella, Bacteroides, and Parabacteroides at the genus level (p < 0.05). Depending on DP, HPI exerts the more positive regulation on liver injury and gut microbiota dysfunction than LPI.


Asunto(s)
Disbiosis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Inulina/administración & dosificación , Inulina/química , Hígado/lesiones , Obesidad/tratamiento farmacológico , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos/análisis , Disbiosis/genética , Disbiosis/metabolismo , Disbiosis/microbiología , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , FN-kappa B/genética , FN-kappa B/metabolismo , Obesidad/genética , Obesidad/metabolismo , Obesidad/microbiología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Polimerizacion
9.
J Agric Food Chem ; 68(4): 1007-1014, 2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-31914311

RESUMEN

Induction of beige adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity because beige adipocytes release excess energy via uncoupling-protein-1-associated thermogenesis. In this study, we investigated how artepillin C (ArtC) promotes thermogenesis in vivo. We demonstrated that 28 day administration of ArtC (10 mg/kg of body weight) to mice significantly induced thermogenesis in beige adipocytes in inguinal WAT (iWAT) and suppressed reductions in core body temperature induced by cold exposure at 4 °C. Moreover, ArtC-induced thermogenesis in iWAT was significantly inhibited by treatment with a creatine metabolism inhibitor, and ArtC significantly upregulated the expression of creatine-metabolism-related enzymes in the thermogenic pathway. These results indicate that ArtC induces thermogenesis in beige adipocytes in iWAT, and the observed ArtC-induced thermogenesis is associated with the creatine-metabolism-related thermogenic pathway, which is characteristically observed in beige adipocytes.


Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Creatina/metabolismo , Obesidad/tratamiento farmacológico , Fenilpropionatos/administración & dosificación , Própolis/análisis , Termogénesis/efectos de los fármacos , Adipocitos Beige/efectos de los fármacos , Adipocitos Beige/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Temperatura Corporal , Brasil , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Obesidad/fisiopatología , Própolis/administración & dosificación
10.
Int J Vitam Nutr Res ; 90(1-2): 169-178, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30829138

RESUMEN

Nowadays, overweight and obesity are major epidemic health problems that can bring about some other health issues such as cardiovascular disease which is the first cause of mortality worldwide. Thylakoids are disc-like membranes responsible for photosynthetic light reactions in chloroplasts of green plants. Although only a few animal and human studies have been conducted regarding the impact of thylakoids on overweight- and obesity-related factors, all of them have resulted in positive outcomes. These outcomes are as follows: increment of satiety response; suppression of hunger sensations, particularly hedonic hunger; reduction of body weight and fat; promotion of glucose homeostasis; decrease in serum lipids; attenuation of oxidative stress and inflammation; and modulation of gut microbiota, notably by increasing some helpful bacteria such as Lactobacillus reuteri. It seems that some of these useful effects are related to retarded absorption of dietary fat and carbohydrate caused by thylakoids. There is still a need for more well-designed studies.


Asunto(s)
Obesidad , Tilacoides , Animales , Peso Corporal , Suplementos Dietéticos , Humanos , Obesidad/dietoterapia , Obesidad/tratamiento farmacológico , Sobrepeso , Tilacoides/química
11.
Food Chem Toxicol ; 135: 110982, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31747621

RESUMEN

With epidemic of obesity, it affects aspects of female reproduction. Genistein could ameliorate obesity in people and animals, but might exert adverse effects on the female reproductive system. To evaluate the effects of fetal and neonatal genistein exposure on the ovarian health of F1 obese female mice with obesity induced by high-fat diet after weaning, we simulated a diet-induced obesity model to observe and determine biological effects of genistein exposure on the ovarian follicle of overfed female mice. Results showed that F1 female mice with obesity induced by high-fat diet significantly prolonged the estrus cycle, disrupted sex hormonal balance and ovarian follicle development after they were exposed to 25 mg/kg b.w./day of genistein during the fetal and neonatal stages. Genistein significantly up-regulated the ovarian mRNA expression of estrogen receptor beta in F1 obese female mice, and high-fat diet influenced the ovarian mRNA expression of estrogen receptor alpha, luteinizing hormone receptor and follicle-stimulating hormone receptor. Hence, genistein exposure from the fetal stage might increase the risk of reproductive diseases in obese females in later life. Thus, the long-term risks of genistein to obese females should be thoroughly assessed.


Asunto(s)
Dieta Alta en Grasa , Genisteína/efectos adversos , Obesidad/tratamiento farmacológico , Folículo Ovárico/efectos de los fármacos , Animales , Animales Recién Nacidos , Estradiol/metabolismo , Receptor beta de Estrógeno/genética , Ciclo Estral/efectos de los fármacos , Femenino , Feto/efectos de los fármacos , Hormona Folículo Estimulante/metabolismo , Expresión Génica/efectos de los fármacos , Hormona Luteinizante/metabolismo , Ratones Endogámicos ICR , Obesidad/metabolismo , Folículo Ovárico/embriología , Folículo Ovárico/patología , Embarazo , ARN Mensajero/metabolismo
12.
Expert Opin Pharmacother ; 21(3): 275-285, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31790314

RESUMEN

Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases. Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.Areas covered: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.Expert opinion: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects. Like most of the other medications currently available for obesity, liraglutide has some common adverse effects, although generally not serious ones. Liraglutide has additional benefits in reducing cardiovascular events in patients with T2DM but the cost and the need for daily injections may limit its use in obesity. Newer GLP-1RAs, such as semaglutide, or other drugs in development for obesity may have advantages over liraglutide.


Asunto(s)
Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Obesidad/tratamiento farmacológico , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/uso terapéutico , Humanos
13.
Expert Rev Clin Pharmacol ; 13(1): 53-64, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31770497

RESUMEN

Introduction: Obesity poses a significant increase in morbidity and mortality and thus five anti-obesity drugs have been approved currently by US FDA. Several phase 3 trials have shown a significant improvement in cardio-metabolic profile including significant weight reduction with these agents compared to placebo.Areas covered: We systematically searched the database of PubMed, Embase, The Cochrane Library and The ClinicalTrials.gov up to 30 September 2019 and retrieved all the randomized controlled trials (RCTs) that were conducted with these five drugs for ≥1 year and explicitly reported their efficacy versus placebo. Subsequently, we have conducted the meta-analysis to primarily study the effect of these anti-obesity drugs on weight reduction. We additionally reviewed the effect of these drugs on other cardio-metabolic parameters including key adverse events.Expert opinion: This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ∆ -3.07 Kg, 95% CI, -3.76 to -2.37), phentermine plus topiramate (N = 2985; ∆ -9.77 Kg; 95% CI, -11.73 to -7.81), lorcaserin (N = 16,856; ∆ -3.08 Kg; 95% CI, -3.49 to -2.66), naltrexone plus bupropion (N = 3239; ∆ -4.39 Kg; 95% CI, -5.05 to -3.72) and liraglutide (N = 4978; ∆ -5.25 Kg; 95% CI, -6.17 to -4.32), compared to placebo (all p < 0.00001).


Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Fármacos Antiobesidad/efectos adversos , Humanos , Obesidad/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Expert Opin Pharmacother ; 21(1): 21-28, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31693425

RESUMEN

Introduction: Obesity is a chronic disease caused by dysfunctional neurohormonal systems that result in excess weight, adiposopathy, and increased risk for many comorbidities including cardiovascular disease, type 2 diabetes, and certain types of cancer. Lorcaserin is a serotonergic agonist specific to the 5HT2C receptor that is FDA-approved for the long-term management of obesity in adults with BMI>30 kg/m2 or BMI>27 kg/m2 and at least one weight-related comorbidity.Areas covered: The authors review the pharmacodynamics and pharmacokinetic properties of lorcaserin alongside updates on serotonin's mechanism of action in the central nervous system. The efficacy of lorcaserin in the management of obesity, its related comorbidities, and potential therapeutic applications are also discussed.Expert opinion: The future of obesity management requires a multimodal and personalized approach. The high medical complexity of patients warrants polypharmacotherapy to achieve their metabolic goals. Lorcaserin has proven efficacy and safety in the treatment of obesity and its weight-related comorbidities including type 2 diabetes, cardiovascular disease, and chronic kidney disease. New evidence elucidating its effects on dopaminergic pathways and on glucose homeostasis expands its prospective uses.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Benzazepinas/administración & dosificación , Obesidad/tratamiento farmacológico , Adulto , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedad Crónica , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Neoplasias/tratamiento farmacológico , Obesidad/complicaciones , Pérdida de Peso/efectos de los fármacos
15.
J Agric Food Chem ; 68(1): 4-16, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31829005

RESUMEN

Obesity has an important influence on health conditions, causing a multitude of complications and comorbidities, and drug therapy is considered to be one of the treatment strategies. Nowadays, there is increasing interest in the study of intestinal microbiota regulation of obesity; also, an increasing number of agricultural and sideline products have been found to have anti-obesity potential. In the present review, we summarize an overview of current known and potential anti-obesity oligosaccharides and their molecular structures. We describe their anti-obesity potential activity and the molecular structure associated with this activity, the regulation of intestinal microbiota composition and its mechanism of action, including regulation of the short-chain fatty acid (SCFA) pathway and altering bile acid (BA) pathway. This review will provide new ideas for us to develop new anti-obesity functional foods.


Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Obesidad/tratamiento farmacológico , Oligosacáridos/administración & dosificación , Animales , Fármacos Antiobesidad/química , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal , Humanos , Obesidad/metabolismo , Obesidad/microbiología , Oligosacáridos/química , Prebióticos/administración & dosificación , Prebióticos/análisis
16.
Eur J Med Chem ; 187: 111948, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31877540

RESUMEN

The aldehyde oxidases (AOXs) are a small sub-family of cytosolic molybdo-flavoenzymes, which are structurally conserved proteins and broadly distributed from plants to animals. AOXs play multiple roles in both physiological and pathological processes and AOX inhibition is of increasing significance in the development of novel drugs and therapeutic strategies. This review provides an overview of the evolution and the action mechanism of AOX and the role of each domain. The review provides an update of the polymorphisms in the human AOX. This review also summarises the physiology of AOX in different organs and its role in drug metabolism. The inhibition of AOX is a promising therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis.


Asunto(s)
Aldehído Oxidasa/antagonistas & inhibidores , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Neoplasias/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Obesidad/tratamiento farmacológico , Aldehído Oxidasa/metabolismo , Esclerosis Amiotrófica Lateral/metabolismo , Animales , Antineoplásicos/química , Inhibidores Enzimáticos/química , Humanos , Neoplasias/metabolismo , Fármacos Neuroprotectores/química , Obesidad/metabolismo
17.
Einstein (Sao Paulo) ; 18: eAO4876, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-31576909

RESUMEN

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.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Dieta Alta en Grasa , Obesidad/tratamiento farmacológico , Sericinas/uso terapéutico , Tejido Adiposo/patología , Animales , Fármacos Antiobesidad/farmacología , Peso Corporal/efectos de los fármacos , Colesterol/análisis , Dieta Alta en Grasa/efectos adversos , Ingestión de Alimentos/efectos de los fármacos , Hígado Graso/patología , Tránsito Gastrointestinal/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/etiología , Obesidad/fisiopatología , Reproducibilidad de los Resultados , Sericinas/farmacología , Factores de Tiempo , Resultado del Tratamiento , Triglicéridos/análisis , Aumento de Peso/efectos de los fármacos
18.
Expert Opin Investig Drugs ; 29(1): 63-71, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31847611

RESUMEN

Introduction: Obesity is compounded by a neurobiology that is resistant to weight loss. Therefore, the development of pharmacotherapies to address the pathology underlying the dysregulation of energy homeostasis is critical.Areas covered: This review examines selected clinical trial evidence for the pharmacologic treatment of obesity and provides an expert opinion on anti-obesity drug development. The article includes the outcomes of anti-obesity medications that have been evaluated in clinical trials but have not yet received approval from the U.S. Food and Drug Administration. The mechanisms of action of glucagon-like peptide-1 agonists and co-agonists, diabetes medications being investigated for weight loss, and medications acting on the central nervous system as well as peripherally are reviewed. A search was conducted on PubMed using the terms 'Obesity AND Medications' restricted to clinical trials reported in English. Using similar terms, a search was also conducted on ClinicalTrials.gov.Expert opinion: The goal of anti-obesity therapy is finding compounds that are effective and have minimal side effects. Combining medications targeting more than one of the redundant mechanisms driving obesity increases efficacy. However, targeting peripheral mechanisms to overcome the trickle-down effects of centrally acting drugs may be the key to success in treating obesity.


Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Desarrollo de Medicamentos , Obesidad/tratamiento farmacológico , Animales , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/farmacología , Metabolismo Energético/fisiología , Humanos , Obesidad/fisiopatología , Pérdida de Peso/efectos de los fármacos
19.
Phytomedicine ; 66: 153129, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31794911

RESUMEN

BACKGROUND: Phyllanthus emblica L. (Indian gooseberry) is widely used in the Ayurveda for thousands of years to treat health complications including disorders of the immune system, diabetes, and obesity. PURPOSE: For the first time, our study aims to demonstrate the molecular mechanisms of the fruit extract of Phyllanthus emblica (PEFE) involved in the promotion of fat cell apoptosis and alleviation of adipogenesis. METHODS: The active constituents from PEFE were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). We carried out the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects of PEFE using 3T3-L1 pre-adipocytes. The colonogenic assay was carried out to determine the inhibitory effect of 3T3-L1 adipocytes after PEFE treatment. In addition, inhibition of pancreatic lipase activity was performed and the lipolytic activity of PEFE and digallic acid was compared with the well-known standard drug orlistat. Besides, the molecular interaction and ligand optimization between digallic and adipogenesis/apoptosis markers were also carried out. Furthermore, to confirm fat cell apoptosis we have used several detection methods that includes Hoechst staining, PI staining, Oil staining and qPCR respectively. RESULTS: Digallic acid was identified as a major component in the PEFE. The IC50 values of digallic acid and PEFE were found to be 3.82 µg/ml and 21.85 µg/ml respectively. PEFE and digallic acid showed significant anti-lipolytic activity compared to the standard drug orlistat. In the mature adipocytes, PEFE significantly decreased triglyceride accumulation by downregulating adiponectin, PPARγ, cEBPα, and FABP4 respectively. We further analyzed the expression of apoptosis related genes upon PEFE treatment. Apoptotic process initiated through upregulation of BAX and downregulation of BCL2 resulting in an increased caspase-3 activity. In addition, we have also confirmed the apoptosis and DNA fragmentation in 3T3-L1 cells using Hoechst, PI and TUNEL assays. CONCLUSION: PEFE negatively regulates adipogenesis by initiating fat cell apoptosis and therefore it can be considered as a potential herbal medicinal product for treating obesity.


Asunto(s)
Fármacos Antiobesidad/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Phyllanthus emblica/química , Fitoterapia , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Frutas/química , Humanos , Lipólisis/efectos de los fármacos , Ratones , Extractos Vegetales/química , Triglicéridos/metabolismo
20.
J Ethnopharmacol ; 247: 112273, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-31586692

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.


Asunto(s)
Cucurbitaceae/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Glicósidos/farmacología , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Obesidad/tratamiento farmacológico , Triterpenos/farmacología , Administración Oral , Animales , Glucemia/análisis , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Fraccionamiento Químico , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Dieta Alta en Grasa/efectos adversos , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/uso terapéutico , Péptido 1 Similar al Glucagón/metabolismo , Glicósidos/análisis , Glicósidos/aislamiento & purificación , Glicósidos/uso terapéutico , Humanos , Hipoglucemiantes/análisis , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/uso terapéutico , Hipolipemiantes/análisis , Hipolipemiantes/aislamiento & purificación , Hipolipemiantes/uso terapéutico , Insulina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Obesidad/sangre , Obesidad/etiología , Ratas , Estreptozocina/toxicidad , Triterpenos/análisis , Triterpenos/aislamiento & purificación , Triterpenos/uso terapéutico
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