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1.
Chem Biol Interact ; 330: 109167, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603660

RESUMO

Recently, it has been shown that drimane-type sesquiterpenoids isolated from Zygogynum pancheri, a species native to New Caledonia, possessed significant α-amylase inhibitory activities. To further explore their antidiabetic potential, we investigated the effect of 1ß-O-(E-cinnamoyl)-6α-hydroxy-9epi-polygodial (D) and 1ß-E-O-p-methoxycinnamoyl-bemadienolide (L), two of the most active compounds of the series, on diabetic model rats. Compounds D and L (2 mg kg/day) were daily and orally administrated for 30 days to streptozotocin (STZ) (150 mg/kg) induced male diabetic Wistar rats. Animals were allocated into five groups of six rats. Comparatively to diabetic rats, treatments with D and L compounds were able to significantly (P < 0.05) decrease Fasting Blood Glucose (FBG) (70.15%, 71.02%), serum total cholesterol (46.27% and 39.38%), triglycerides (56.60% and 58.15%), creatinine (37.31% and 36.49%) and uric acid levels (67.76% and 69.68%), respectively. Compounds D and L also restored the altered plasma enzyme (aspartate aminotransferase, AST (47.83% and 43.20%), alanine aminotransferase, ALT (49.76% and 48.35%, alkaline phosphatase, ALP (72.78% and 73.21%)) and lactate dehydrogenase, LDH (47.95% and 53.93%) levels to near normal, respectively. Administration of Glymepiride, significantly (p < 0.05) reduced FBG (73.94%) in STZ induced diabetic rats. Additionally, the compounds D and L exhibited inhibitory effects in vivo on lipase activity of diabetic rats (54.83% and 52.25%), respectively. The outcomes of this study suggested that these two drimanes could be considered as efficient hypoglycemic, hypolipidemic and antiobesity agents for diabetes management and its complications.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação , Animais , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Masculino , Nova Caledônia , Extratos Vegetais/química , Sesquiterpenos Policíclicos/farmacologia , Ratos , Ratos Wistar , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Winteraceae/química
2.
Obesity (Silver Spring) ; 28(6): 1023-1030, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441476

RESUMO

OBJECTIVE: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon. METHODS: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively. RESULTS: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB. CONCLUSIONS: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Derivação Gástrica/métodos , Fentermina/uso terapêutico , Topiramato/uso terapêutico , Ganho de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/farmacologia , Período Pós-Operatório , Estudos Retrospectivos , Topiramato/farmacologia
3.
Food Chem ; 320: 126648, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234657

RESUMO

High circulating branched-chain amino acid (BCAA) levels can be diagnosis indicators for obesity. Luffa cylindrica (luffa) is one of vegetables against obesity. However, whether the anti-obesity of luffa is associated with BCAA metabolism and gut microbiota remains unknown. Here, we used conventionally raised diet-induced obese (DIO) mice to prove dietary luffa could reduce higher circulating BCAA levels and upregulate the tissue-specific expressions of BCAA-catabolizing enzymes. Meanwhile, dietary luffa selectively decreased the relative abundances of g_Enterortabdus, g_Eubacterium_xylanophilum_group and g_Butyricicoccus that exhibited significantly positive correlations with BCAA levels, BMI and HOMA-IR. Bacterial functionality prediction indicated dietary luffa potentially inhibited bacterial BCAA biosynthesis for reducing BCAAs supplementation. More importantly, dietary luffa had no impacts on BCAA catabolism in germ-free-mimic DIO mice. Thus, dietary luffa improved BCAA dysfunction via gut microbiota to attenuate obesity. This study offers a novel insight into dietary intervention against obesity from the aspect of gut microbiota-amino acid metabolism.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Fármacos Antiobesidade/farmacologia , Microbioma Gastrointestinal/fisiologia , Luffa , Obesidade/dietoterapia , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia
4.
Arch Biochem Biophys ; 686: 108365, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315651

RESUMO

Pelargonidin is a natural compound that exists widely in fruits, and exerts antioxidant, anti-atherosclerotic, anti-inflammatory, anti-hyperglycemic, and anti-diabetic activities. However, there have not been any studies concerning its anti-obesity potential to date. Therefore, we evaluated the anti-obesity potential of pelargonidin via inhibition of adipogenesis in 3T3-L1 cells. The cellular oil droplet content was decreased to 68.14%, 56.75%, and 48.39% and triglyceride accumulation decreased to 74.53%, 61.54%, and 47.86% after incubation with 5 µM, 10 µM, and 20 µM pelargonidin, respectively, when compared with DMSO group. Furthermore, pelargonidin treatment led to decrease in glucose consumption. Western blot assay illustrated that the expression of PPAR-γ was suppressed to 63.25%, 47.52%, and 21.23% after incubation with 5 µM, 10 µM, and 20 µM pelargonidin when compared with DMSO group. Then, we measured the expression of some target proteins of PPAR-γ, and found that pelargonidin decreased the expressions of HMGCR, LPL, Glut4, and A-FABP. Besides, the result of Luciferase Reporter Assay indicated that pelargonidin inhibited PPAR-γ transcription activity. These results indicated that pelargonidin exerts anti-adipogenic activity in 3T3-L1 cells through inhibition of PPAR-γ signaling pathway, and pelargonidin could be used as a potential anti-obesity agent.


Assuntos
Adipogenia/efeitos dos fármacos , Antocianinas/farmacologia , Fármacos Antiobesidade/farmacologia , PPAR gama/metabolismo , Células 3T3-L1 , Animais , Antocianinas/metabolismo , Fármacos Antiobesidade/metabolismo , Regulação para Baixo/efeitos dos fármacos , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Camundongos , Triglicerídeos/genética , Triglicerídeos/metabolismo
5.
PLoS One ; 15(4): e0231815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348327

RESUMO

Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.


Assuntos
Fármacos Antiobesidade/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Obesidade/tratamento farmacológico , alfa-Amilases Pancreáticas/antagonistas & inibidores , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/química , Metabolismo dos Carboidratos/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Colestenonas/química , Colestenonas/farmacologia , Medicamentos de Ervas Chinesas/química , Ensaios Enzimáticos , Flavanonas/química , Flavanonas/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Obesidade/metabolismo , alfa-Amilases Pancreáticas/química , alfa-Amilases Pancreáticas/metabolismo , Suínos
6.
Rev Med Suisse ; 16(687): 573-577, 2020 Mar 25.
Artigo em Francês | MEDLINE | ID: mdl-32216179

RESUMO

Obesity is a chronic disease that requires a complex treatment. Establishing a balanced diet and regular physical activity is not always simple, especially in the long term. There are multiple factors (biological and psychological) favoring weight gain, often limiting the effectiveness of lifestyle approaches. Pharmacology offers us another therapeutic option with new molecules effective for weight loss. Bariatric surgery is also effective, but it is not without risks, especially if the patients have not been adequately prepared for this procedure. Furthermore, these approaches should always be proposed as complementary to lifestyle changes. This article summarizes the different treatments for obesity and highlights the importance of a multidisciplinary management and proper patient education.


Assuntos
Exercício Físico/fisiologia , Obesidade/prevenção & controle , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Dieta Saudável , Exercício Físico/psicologia , Humanos , Obesidade/psicologia , Perda de Peso/efeitos dos fármacos
7.
Food Chem ; 318: 126474, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151922

RESUMO

Excessive energy intake, poor physical exercise and genetics/epigenetics are instrumental for the development of obesity. Because of rapidly emerging evidences related to off-target effects and toxicity of anti-obesity drugs, there is a need to search for more effective and targeted drugs for treatment of obesity. Substantial studies have found the nutritional effects of dietary saponins (bio-detergents) in terms of decreasing the synthesis of lipids, suppressing adipogenesis, inhibiting intestinal absorption of lipids, and promoting fecal excretion of bile acids and triglycerides. Dietary saponin have been approved as potent pancreatic lipase inhibitors, disaccharidase enzyme inhibitors, antagonistic to in vitro lipogenesis and in vivo appetite suppressants, antioxidants, immune-regulators, prevent fatty liver formation, protects epithelial vasculature and regulate body weight. Many dietary saponins, such as sibutramine, morgoside, sessiloside, soysaponin B, and diosgenin, have treatment potential against the development of obesity. Excellent scientific achievements have been developed for a better understanding the mechanism of saponins in preventing obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Obesidade/prevenção & controle , Saponinas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Inibidores Enzimáticos/farmacologia , Humanos , Lipase/antagonistas & inibidores , Obesidade/dietoterapia , Saponinas/química
8.
Curr Pharm Biotechnol ; 21(11): 1099-1106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32188382

RESUMO

BACKGROUND: Chlorogenic Acid (CA) has diverse, recognized health effects. OBJECTIVE: This study aimed to explore the effects of CA on fat reduction and the underlying mechanism of these effects. MATERIALS AND METHODS: First, we established a Monosodium Glutamate (MSG)-induced obesity mouse model and subjected the mice to 4 weeks of CA gavage. Then, we established an oleic acidinduced model of human fatty liver in HepG2 cells, and administered a CA intervention to the cells for 48 h. Finally, we used Oil red O staining, biochemical detection kits, RT-PCR and Western blot analysis to evaluate the effects of CA on fat reduction and on related pathways. RESULTS: The CA treatment could reduce fat accumulation in the liver and reduce blood lipid levels. In addition, CA decreased the mRNA and protein levels of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α) and Uncoupling Protein 1 (UCP1) in the MSG-induced obesity mouse model and the oleic acid-induced HepG2 cells. CONCLUSION: Based on the above results, we deduced that CA could reduce body weight and fat deposition in vitro and in vivo and that the mechanism may be related to the PGC-1α/UCP-1 pathway. CA can be developed as a drug to lower blood lipids and to treat obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Ácido Clorogênico/farmacologia , Fígado Gorduroso/tratamento farmacológico , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/uso terapêutico , Ácido Clorogênico/uso terapêutico , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glutamato de Sódio/metabolismo , Proteína Desacopladora 1/metabolismo
9.
Obesity (Silver Spring) ; 28(3): 529-536, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090517

RESUMO

OBJECTIVE: Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg. METHODS: The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE) IBT was a 56-week, randomized, double-blind, placebo-controlled, multicenter trial in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140) as an adjunct to IBT. RESULTS: At week 56, mean weight loss with liraglutide 3.0 mg plus IBT was 7.5% and 4.0% with placebo combined with IBT (estimated treatment difference [95% CI]-3.4% [-5.3% to -1.6%], P = 0.0003). Significantly more individuals on liraglutide 3.0 mg than placebo achieved ≥ 5% weight loss (61.5% vs. 38.8%; odds ratio [OR] 2.5% [1.5% to 4.1%], P = 0.0003), > 10% weight loss (30.5% vs. 19.8%; OR 1.8% [1.0% to 3.1%], P = 0.0469), and > 15% weight loss (18.1% vs. 8.9%; OR 2.3% [1.1% to 4.7%], P = 0.0311). Liraglutide 3.0 mg in combination with IBT was well tolerated, with no new safety signals identified. CONCLUSIONS: In a primary care setting, Centers for Medicare and Medicaid Services-based IBT produced clinically meaningful weight loss at 56 weeks, enhanced by the addition of liraglutide 3.0 mg.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Terapia Comportamental/métodos , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Método Duplo-Cego , Feminino , Humanos , Liraglutida/farmacologia , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Resultado do Tratamento , Estados Unidos
10.
PLoS One ; 15(1): e0227637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929574

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/farmacologia , Hesperidina/farmacologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Obesidade/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Fármacos Antiobesidade/química , Dieta Hiperlipídica , Modelos Animais de Doenças , Quimioterapia Combinada , Hesperidina/química , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Inflamação/metabolismo , Inflamação/patologia , Leptina/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Obesidade/metabolismo , Obesidade/patologia , Orlistate/química , Orlistate/farmacologia , Ratos Wistar
11.
Phytochemistry ; 171: 112231, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901473

RESUMO

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.


Assuntos
Compostos Fitoquímicos/farmacologia , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
12.
Phytother Res ; 34(6): 1282-1290, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31989713

RESUMO

Obesity is a worldwide epidemic and is one of the factors involved in the etiology of type 2 diabetes mellitus. Obesity induces low-grade inflammation and oxidative stress. The treatment for obesity involves changes in diet, physical activity, and even medication and surgery. Currently, the use of nutraceutical compounds is associated with health benefits. Ginger and avocado are used for many people all around the world; however, its effect as a nutraceutical compound is less known by the general population. For this reason, we searched information of the literature to point its effects on distinct mechanisms of defense against the obesity its comorbidities. The present review aimed showing that these nutraceuticals may be useful in obesity treatment. Reports have shown that ginger and avocado induce antioxidant and anti-inflammatory effects by improving enzymatic activity and modulating obesity-related impairments in the anti-inflammatory system in different tissues, without side effects. Furthermore, ginger and avocado were found to be effective in reversing the harmful effects of obesity on blood lipids. In conclusion, on the basis of the positive effects of ginger and avocado in in vitro, animal, and human studies, these nutraceuticals may be useful in obesity treatment.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais/análise , Gengibre/química , Obesidade/tratamento farmacológico , Persea/química , Animais , Fármacos Antiobesidade/farmacologia , Humanos
13.
Int J Mol Sci ; 21(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936890

RESUMO

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.


Assuntos
Adipócitos/metabolismo , Fármacos Antiobesidade/farmacologia , Diferenciação Celular/efeitos dos fármacos , Ergosterol/análogos & derivados , Metabolismo dos Lipídeos/efeitos dos fármacos , Reishi/química , Células 3T3-L1/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipocinas , Animais , Fármacos Antiobesidade/uso terapêutico , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ergosterol/química , Ergosterol/farmacologia , Ergosterol/uso terapêutico , Lipogênese/efeitos dos fármacos , Camundongos , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos
14.
J Sci Food Agric ; 100(6): 2380-2388, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31901136

RESUMO

BACKGROUND: An imbalanced fat or excess energy intake always results in obesity and increased serum/liver lipids, thus leading to metabolic syndromes. Given the bioactive components in black vinegar (BV), such as branched amino acids, phenolic profile, and mineral contents, we investigated the antiobesity effects of BV-based supplements in rats fed a high-fat diet (HFD). RESULTS: HFD (30% fat, w/w) feeding increased (P < 0.05) body weight, weight gains, weights of livers and mesenteric, epididymal, and perirenal adipose tissues, and serum/liver triglyceride levels relative to those of rats fed a normal diet (4% fat, w/w; CON). These increased values were ameliorated (P < 0.05) by supplementing with BV-based supplements but were still higher (P < 0.05) than those of CON rats. The increased areas of perirenal adipocytes in rats fed with an HFD were also decreased (P < 0.05) by supplementing with BV-based supplements, which might result from an upregulation (P < 0.05) of 5'-adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase-1 (CPT1), and uncoupling protein-2 (UCP2) in the perirenal adipose tissues. A similar effect was observed for AMPK, peroxisome proliferator-activated receptor alpha, retinoid X receptor alpha, CPT1, and UCP2 gene and protein levels in livers (P < 0.05). Generally, BV-based supplements increased the fecal triglyceride, cholesterol, and bile acid levels of rats fed with an HFD, which partially contribute to the lipid-lowering effects. Furthermore, BV-based supplements increased (P < 0.05) hepatic Trolox equivalent antioxidant capacity and lowered (P < 0.05) serum/liver thiobarbituric acid reactive substances values in HFD-fed rats. CONCLUSION: In a chronic high-fat dietary habit, the food-grade BV-based supplement is a good daily choice to ameliorate obesity and its associated comorbidities. © 2020 Society of Chemical Industry.


Assuntos
Ácido Acético/administração & dosagem , Ácido Acético/metabolismo , Fármacos Antiobesidade/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Adipócitos , Animais , Antioxidantes , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Metabolismo Energético , Fezes/química , Masculino , Ratos Wistar
15.
Appl Environ Microbiol ; 86(7)2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31953338

RESUMO

The objective of this study was to elucidate the effect of intestinal Akkermansia muciniphila bacteria on fatty liver disease. Five-week-old C57BL/6N mice were administered either phosphate-buffered saline (PBS; control) or A. muciniphila at 108 to 109 CFU/ml, and were fed either a 45% fat diet (high-fat diet [HFD]) or a 10% fat diet (normal diet [ND]) for 10 weeks. After 10 weeks, the mice were euthanized, and blood and tissue samples, including adipose tissue, cecum, liver, and brain, were immediately collected. Biochemical and histological analyses were conducted, and the expression levels of related factors were compared to determine the antiobesity effects of Akkermansia muciniphila The gut microbiome was analyzed in fecal samples. Oral administration of A. muciniphila significantly (P < 0.05) lowered serum triglyceride (TG) and alanine aminotransferase (ALT) levels in obese mice. Compared to the non-A. muciniphila-treated group, the expression of SREBP (regulator of TG synthesis in liver tissue) was decreased in the A. muciniphila-treated group. The expression of IL-6 in the liver of obese mice was decreased following the administration of A. muciniphila Furthermore, alterations in the ratio of Firmicutes to Bacteroidetes and the decrease in bacterial diversity caused by the HFD were restored upon the administration of A. muciniphila These results indicate that A. muciniphila prevents fatty liver disease in obese mice by regulating TG synthesis in the liver and maintaining gut homeostasis.IMPORTANCE This study investigated the effect of Akkermansia muciniphila on fatty liver disease. Although some research about the effects of A. muciniphila on host health has been published, study of the relationship between A. muciniphila administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that A. muciniphila prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver.


Assuntos
Fármacos Antiobesidade/farmacologia , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Triglicerídeos/sangue , Verrucomicrobia/química , Animais , Fármacos Antiobesidade/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
16.
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
17.
Artigo em Inglês | MEDLINE | ID: mdl-31676442

RESUMO

Pancreatic lipase (PNLIP) is a digestive enzyme that is a potential drug target for the treatment of obesity. A better understanding of its regulation mechanisms would facilitate the development of new therapeutics. Recent studies indicate that intestinal lipolysis by PNLIP is reduced by Angiopoietin-like protein 4 (ANGPTL4), whose N-terminal domain (nANGPTL4) is a known inactivator of lipoprotein lipase (LPL) in blood circulation and adipocytes. To elucidate the mechanism of PNLIP inhibition by ANGPTL4, we developed a novel approach, using isothermal titration calorimetry (ITC). The obtained results were compared with those of well-described inhibitors of PNLIP - ε-polylysine (EPL), (-)-epigallocatechin-3-gallate (EGCG) and tetrahydrolipstatin. We demonstrate that ITC allows to investigate PNLIP inhibition mechanisms in complex substrate emulsions and that the ITC-based assay is highly sensitive - the lowest concentration for quantification of PNLIP is 1.5 pM. Combining ITC with surface plasmon resonance and fluorescence measurements, we present evidence that ANGPTL4 is a lipid-binding protein that influences PNLIP activity through interactions with components of substrate emulsions (bile salts, phospholipids and triglycerides), and this promotes the aggregation of triglyceride emulsions similarly to the PNLIP inhibitors EPL and EGCG. In the absence of substrate emulsion, unlike in the case of LPL, ANGPTL4 did not induce the inactivation of PNLIP. Our data also prove that due to various interactions with components of substrate systems, the effect of a PNLIP inhibitor depends on whether its effect is measured in a complex substrate emulsion or in a simple substrate system.


Assuntos
Proteína 4 Semelhante a Angiopoietina/farmacologia , Fármacos Antiobesidade/farmacologia , Calorimetria , Ensaios Enzimáticos/métodos , Lipase/antagonistas & inibidores , Proteína 4 Semelhante a Angiopoietina/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Catequina/análogos & derivados , Catequina/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Lipase/genética , Lipase/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Orlistate/farmacologia , Polilisina/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
18.
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
19.
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
20.
Phytomedicine ; 66: 153129, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794911

RESUMO

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.


Assuntos
Fármacos Antiobesidade/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Phyllanthus emblica/química , Fitoterapia , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Frutas/química , Humanos , Lipólise/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Triglicerídeos/metabolismo
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