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1.
Expert Opin Pharmacother ; 21(11): 1319-1328, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32292094

RESUMO

INTRODUCTION: Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions. AREAS COVERED: This review covers the history of antiobesity drugs, efficacy, and risks of currently approved drugs, limits of their usefulness in clinical practice, gaps in knowledge, methodological limitations of clinical trials, and reasons for underutilization. EXPERT OPINION: In randomized controlled trials, currently approved antiobesity drugs have yielded an average weight loss ranging from approximately 3% to 9% relative to placebo at 1 year. Inadequate inclusion of racial and ethnic minorities and men, and high dropout rates in clinical trials limit generalizability of these findings to clinical practice. Weight loss achieved with antiobesity drugs is generally associated with lowered glycemia, but improvements in blood pressure and lipid measures tend to be marginal. There is limited evidence for sustained weight loss beyond 1 year and for safety and efficacy of antiobesity drugs in children and adolescents, and in post-bariatric surgery patients. None have demonstrated reduction in major adverse cardiovascular events or other significant disease outcomes. Limited health insurance coverage and negative perceptions of physicians have hindered the utilization of antiobesity drugs.


Assuntos
Fármacos Antiobesidade , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adolescente , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Pressão Sanguínea/efeitos dos fármacos , Criança , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Uso de Medicamentos , Humanos , Estilo de Vida , Resultado do Tratamento
2.
Expert Opin Pharmacother ; 21(2): 167-172, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31762335

RESUMO

Introduction: Obesity is considered to be a chronic disease. Currently there are five prescription-only medications on the US market for the long-term management of obesity. However, these medications are underutilized by obese or overweight individuals seeking medical assistance for weight management.Areas covered: This special report provides an overview of the emerging obesity pharmacotherapies based on the data available from recruiting and active phase II/III trials from a registry of clinical trials. The authors also give their expert opinion and provide their future perspectives on the treatment of obesity based on what is known.Expert opinion: Despite obesity being a chronic condition affecting 40% of the US population, there is a low demand for obesity medications in the US market. Although the potential obesity medications that are currently being investigated in phase II/III clinical trials are promising, it is unclear whether the future pharmacotherapies will be enough to meet the health care need.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Depressores do Apetite/administração & dosagem , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Humanos , Estados Unidos , Perda de Peso/efeitos dos fármacos
3.
Expert Rev Clin Pharmacol ; 13(1): 53-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770497

RESUMO

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).


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Fármacos Antiobesidade/efeitos adversos , Humanos , Obesidade/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Agric Food Chem ; 68(1): 4-16, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31829005

RESUMO

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.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Animais , Fármacos Antiobesidade/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Humanos , Obesidade/metabolismo , Obesidade/microbiologia , Oligossacarídeos/química , Prebióticos/administração & dosagem , Prebióticos/análise
5.
Expert Rev Clin Pharmacol ; 13(2): 183-190, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31815555

RESUMO

Background: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin.Research design and methods: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs.Results: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ∆ -3.076 Kg; 95% CI, -3.49 to -2.66; P < 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo.Conclusions: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache.


Assuntos
Benzazepinas/administração & dosagem , Obesidade/tratamento farmacológico , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Benzazepinas/efeitos adversos , Benzazepinas/farmacologia , Peso Corporal/efeitos dos fármacos , Humanos , Obesidade/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Agonistas do Receptor 5-HT2 de Serotonina/efeitos adversos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Perda de Peso/efeitos dos fármacos
6.
Expert Opin Investig Drugs ; 29(1): 63-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31847611

RESUMO

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.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Desenvolvimento de Medicamentos , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Metabolismo Energético/fisiologia , Humanos , Obesidade/fisiopatologia , Perda de Peso/efeitos dos fármacos
7.
Mar Drugs ; 17(11)2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31717668

RESUMO

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases.


Assuntos
Fármacos Antiobesidade/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Obesidade/tratamento farmacológico , Feófitas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Administração Oral , Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/isolamento & purificação , Dieta Hiperlipídica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/fisiopatologia , Ganho de Peso/efeitos dos fármacos
8.
Clin Obes ; 9(6): e12340, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691531

RESUMO

This study examined the effects of intensive behavioural therapy (IBT) for obesity (IBT-alone), IBT plus liraglutide 3.0 mg/day (IBT-liraglutide), and IBT-liraglutide combined with 12 weeks of a portion-controlled diet (Multicomponent) on changes in general health-related (HR) quality of life (QoL) and weight-related QoL. Adults with obesity (79.3% female; 54.0% white; 44.7% black; mean age = 47.6 ± 11.8 years and body mass index = 38.4 ± 4.9 kg/m2 ) were randomized to IBT-alone (n = 50), IBT-liraglutide (n = 50) or Multicomponent (n = 50). General HRQoL was measured with the Short Form-36 (SF-36), and weight-related QoL was assessed with the Impact of Weight on Quality of Life-Lite scale. At week 52, participants in the three groups lost 6.1 ± 1.3%, 11.5 ± 1.3% and 11.8 ± 1.3% of initial body weight, respectively. Both liraglutide-treated groups were significantly more likely than IBT-alone to achieve clinically meaningful improvements in total weight-related QoL. They also both achieved greater improvements than IBT-alone in weight-related public distress and in general mental health, as measured by the SF-36 mental component summary score. Independent of treatment group, greater categorical weight loss was associated with greater improvements in several domains of both general and weight-related QoL. The addition of liraglutide to IBT appeared to improve aspects of both general HRQoL and weight-related QoL.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Terapia Comportamental , Liraglutida/administração & dosagem , Obesidade/terapia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/psicologia , Qualidade de Vida , Perda de Peso/efeitos dos fármacos , Adulto Jovem
9.
Mar Drugs ; 17(9)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540318

RESUMO

This study investigated the anti-obesity effect of a polysaccharide-rich red algae Gelidium amansii hot-water extract (GHE) in high-fat (HF) diet-induced obese hamsters. GHE contained 68.54% water-soluble indigestible carbohydrate polymers. Hamsters were fed with a HF diet for 5 weeks to induce obesity, and then randomly divided into: HF group, HF with 3% guar gum diet group, HF with 3% GHE diet group, and HF with orlistat (200 mg/kg diet) group for 9 weeks. The increased weights of body, liver, and adipose in the HF group were significantly reversed by GHE supplementation. Lower plasma leptin, tumor necrosis factor-α, and interleukin-6 levels were observed in the GHE+HF group compared to the HF group. GHE also increased the lipolysis rate and decreased the lipoprotein lipase activity in adipose tissues. GHE induced an increase in the phosphorylation of AMP-activated protein kinase (AMPK) and the protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and uncoupling protein (UCP)-2 in the livers. The decreased triglyceride and total cholesterol in the plasma and liver were also observed in obese hamsters fed a diet with GHE. These results suggest that GHE exerts a down-regulation effect on hepatic lipid metabolism through AMPK phosphorylation and up-regulation of PPARα and UCP-2 in HF-induced obese hamsters.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Suplementos Nutricionais , Obesidade/dietoterapia , Extratos Vegetais/administração & dosagem , Rodófitas/química , Adenilato Quinase/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mesocricetus , Obesidade/etiologia , Orlistate/administração & dosagem , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 2/metabolismo , Regulação para Cima/efeitos dos fármacos , Água/química
10.
Mar Drugs ; 17(9)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533255

RESUMO

Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as unsaturated alginate oligosaccharides (UAOS) from the enzymatic degradation of Laminaria japonicais, which showed effective anti-obesity effects in a high-fat diet (HFD) mouse model. Compared with acid hydrolyzed saturated alginate oligosaccharides (SAOS), UAOS significantly reduced body weight, serum lipid, including triacylglycerol (TG), total cholesterol (TC) and free fatty acids (FFA), liver weight, liver TG and TC, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, adipose mass, reactive oxygen species (ROS) formation, and accumulation induced in HFD mice. Moreover, the structural differences in ß-d-mannuronate (M) and its C5 epimer α-l-guluronate (G) did not cause significant functional differences. Meanwhile, UAOS significantly increased both AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC) phosphorylation in adipocytes, which indicated that UAOS had an anti-obesity effect mainly through AMPK signaling. Our results indicate that UAOS has the potential for further development as an adjuvant treatment for many metabolic diseases such as fatty liver, hypertriglyceridemia, and possibly diabetes.


Assuntos
Alginatos/administração & dosagem , Fármacos Antiobesidade/administração & dosagem , Aditivos Alimentares/administração & dosagem , Obesidade/dietoterapia , Oligossacarídeos/administração & dosagem , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Alginatos/química , Ração Animal , Animais , Fármacos Antiobesidade/química , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Aditivos Alimentares/química , Humanos , Masculino , Camundongos , Obesidade/etiologia , Oligossacarídeos/química , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
11.
Medicina (Kaunas) ; 55(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505863

RESUMO

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.


Assuntos
Fármacos Antiobesidade/farmacologia , Alho , Gengibre , Hipolipemiantes/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Lovastatina/farmacologia , Óleos Vegetais , Administração Oral , Animais , Fármacos Antiobesidade/administração & dosagem , Emulsões , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Nefropatias/etiologia , Nefropatias/prevenção & controle , Hepatopatias/etiologia , Hepatopatias/prevenção & controle , Lovastatina/administração & dosagem , Masculino , Nanoestruturas , Ratos , Ratos Wistar
12.
BMC Complement Altern Med ; 19(1): 246, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488172

RESUMO

BACKGROUND: Yangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesity in high-fat diet (HFD)-induced obese mice. METHODS: We induced obesity in C57bl/6 J mice using a HFD, and then orally administered 300 mg/kg YST for 6 weeks. We measured body weight, food efficiency, organ and fat weight, serum biochemical parameters, and obesity-related gene expression, and carried out histological analysis at the end of the experimental period. RESULTS: YST significantly reduced the absolute body weight and food efficiency ratio. The serum, aminotransferase, glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels were significantly lower in the YST-treated group than in the control group, whereas the high-density lipoprotein-cholesterol level in the YST-treated group was significantly higher. The YST-treated group also showed a significant reduction in regional fatty tissues and the absolute weight of various organs. We also observed a significantly reduced expression of AP2/FABP4, C/EBP-ß, leptin, and SREBP1c/ADD1 mRNA, and significantly increased expression of UCP-2 and adiponectin mRNA in adipose tissue in the YST-treated group. YST also decreased the lipid droplet size and lipid accumulation in the liver, as well as adipocyte size in epididymal adipose tissue. At the dose tested, YST was non-toxic to the liver and kidneys of the mice. CONCLUSION: The results imply that YST has anti-obesity effects in obesity-induced mice. Although the number of experimental animals was limited and the drug effects concern mice, rather than humans, which have different constitutions, the study has valuable implications with respect to the general effects of YST.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Fármacos Antiobesidade/química , Peso Corporal/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , HDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Leptina/genética , Leptina/metabolismo , Masculino , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Extratos Vegetais/química , Plantas Medicinais/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
13.
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
14.
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
15.
Expert Opin Drug Discov ; 14(11): 1151-1159, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31355685

RESUMO

Introduction: Obesity is a global pandemic and new pharmacotherapies which combine weight loss efficacy, long-term safety, and reversal of metabolic co-morbidities are sorely needed. Gut hormones play key roles in regulating satiety and metabolism, and are natural candidates for therapeutic development. Areas covered: The authors discuss recent drug developments for the treatment of obesity using gut hormones. The review was based on a search of PubMed using keywords 'obesity' AND ('therapy' OR 'pharmacotherapy' OR 'gut hormones' OR 'analogues'), limited to the last 10 years. Expert opinion: Analogues of glucagon-like peptide (GLP-1) have been developed for obesity but so far do not provide enough weight loss. Bariatric surgery increases the post-prandial secretion of multiple gut hormones, leading to beneficial effects on weight loss and metabolism. This recognition has led to poly-agonist strategies: GLP-1/glucagon or GLP-1/glucose-dependent insulinotropic peptide (GIP) dual agonism, or even GLP-1/glucagon/GIP triple agonism. New delivery approaches include peptide-conjugate therapies that target key metabolic tissues. Practicable methods for oral delivery of peptide gut hormones are also close to market, expanding the potential market for these treatments. Anti-obesity therapy is therefore poised for an exciting phase, and it will be interesting to see which of these will eventually prevail.


Assuntos
Fármacos Antiobesidade/farmacologia , Descoberta de Drogas/métodos , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/administração & dosagem , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos/métodos , Hormônios Gastrointestinais/administração & dosagem , Hormônios Gastrointestinais/metabolismo , Hormônios Gastrointestinais/farmacologia , Humanos , Perda de Peso/efeitos dos fármacos
16.
Nutrients ; 11(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277416

RESUMO

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop 'functional' foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or 'satiety' peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating 'thresholds' of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin 'satiety' peptides for weight loss remains a significant challenge.


Assuntos
Regulação do Apetite , Ingestão de Alimentos , Metabolismo Energético , Comportamento Alimentar , Hormônios Peptídicos/metabolismo , Resposta de Saciedade , Perda de Peso , Fármacos Antiobesidade/administração & dosagem , Colecistocinina/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Infusões Parenterais , Masculino , Hormônios Peptídicos/administração & dosagem , Peptídeo YY/metabolismo , Transdução de Sinais , Perda de Peso/efeitos dos fármacos
17.
J Endocrinol ; 242(2): 79-89, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31137012

RESUMO

Obesity-associated chronic inflammation in adipose tissue is partly attributed to hypoxia with insufficient microcirculation. Previous studies have shown that exenatide, a glucagon-like peptide 1 (GLP-1) receptor agonist, plays an anti-inflammatory role. Here, we investigate its effects on inflammation, hypoxia and microcirculation in white adipose tissue of diet-induced obese (DIO) mice. DIO mice were injected intraperitoneally with exenatide or normal saline for 4 weeks, while mice on chow diet were used as normal controls. The mRNA and protein levels of pro-inflammatory cytokines, hypoxia-induced genes and angiogenic factors were detected. Capillary density was measured by laser confocal microscopy and immunochemistry staining. After 4-week exenatide administration, the dramatically elevated pro-inflammatory cytokines in serum and adipose tissue and macrophage infiltration in adipose tissue of DIO mice were significantly reduced. Exenatide also ameliorated expressions of hypoxia-related genes in obese fat tissue. Protein levels of endothelial markers and pro-angiogenic factors including vascular endothelial growth factor and its receptor 2 were augmented in accordance with increased capillary density by exenatide in DIO mice. Our results indicate that inflammation and hypoxia in adipose tissue can be mitigated by GLP-1 receptor agonist potentially via improved angiogenesis and microcirculation in obesity.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Exenatida/farmacologia , Inflamação/prevenção & controle , Microcirculação/efeitos dos fármacos , Obesidade/prevenção & controle , Tecido Adiposo Branco/irrigação sanguínea , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Exenatida/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Hipóxia/genética , Hipóxia/metabolismo , Inflamação/genética , Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos Endogâmicos C57BL , Microcirculação/genética , Microcirculação/fisiologia , Obesidade/etiologia , Obesidade/genética
18.
Eur J Pharm Sci ; 135: 1-11, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31067495

RESUMO

Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid) hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media) and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.


Assuntos
Fármacos Antiobesidade/química , Argila/química , Lipase/antagonistas & inibidores , Lipídeos/química , Nanopartículas/química , Obesidade/tratamento farmacológico , Orlistate/química , Compostos de Alumínio/química , Fármacos Antiobesidade/administração & dosagem , Suplementos Nutricionais , Digestão , Ácidos Graxos/metabolismo , Humanos , Hidrólise , Absorção Intestinal , Lipase/química , Lipólise , Compostos de Magnésio/química , Orlistate/administração & dosagem , Tamanho da Partícula , Silicatos/química , Propriedades de Superfície
19.
J Med Food ; 22(7): 741-751, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120370

RESUMO

The prevalence of obesity is expanding rapidly worldwide, making the disease a global burden with limited treatment options. The current obesity drug development trends suggest the possibility of reducing weight and reverse metabolic disturbances of obesity by controlling appetite. In this study, we screened more than 8000 plants from our plant library for the cannabinoid (CB1) receptor antagonists and identified Morus alba as a lead medicinal plant. Kuwanon G and Albanin G were isolated and identified from root-barks of Morus alba with 92% and 96% CB1 receptor ligand binding inhibitory activity, respectively. The bioflavonoid standardized extract was tested in the acute food intake study in rats at oral doses of 250 and 500 mg/kg for its appetite suppression activity. Diet-induced obesity in the C57BL/6J mice was used to evaluate the long-term food intake reduction activity and effect on the weight loss administered orally at 250 and 500 mg/kg for 7 weeks. Statistically significant and dose-dependent reduction in food intake was observed in both acute and long-term studies for the extract. Food intake reductions of 58.6% and 44.8% at 250 mg/kg and 50.1% and 44.3% at 500 mg/kg were observed at 1 and 2 h postfood provision, respectively. A 20% reduction in daily calorie intake was observed in the long-term study. Obese mice treated with the high dose of Morus root-bark extract showed 10.4 g (22.5%) and 7.1 g (16.5%) loss in body weight compared with the vehicle-treated obese animals (at week 7) and baseline, respectively. Statistically significant reductions in biochemical markers and visceral fat deposit were also observed. These results demonstrated that Morus alba extracts enriched in Kuwanon G, and Albanin G could be used alone to control appetite, manage body weight, and improve metabolic syndromes.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Apetite/efeitos dos fármacos , Morus/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Animais , Fármacos Antiobesidade/química , Ingestão de Alimentos/efeitos dos fármacos , Flavonoides/administração & dosagem , Flavonoides/análise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia , Casca de Planta/química , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Perda de Peso/efeitos dos fármacos
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