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1.
J Obes ; 2021: 9968730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336274

RESUMO

Background: Some anorexic agents are used to fraudulent augmentation herbal weight loss formulations. This study was designed to evaluate the potential existence of illicit substances in 63 herbal weight loss formulations collected from local apothecaries in Hamadan, Iran. Methods: The thin-layer chromatography method was applied for the primary screening of potential illicit substances in the samples. The positive samples were analyzed using an isocratic high-performance liquid chromatography method. Results: The results showed that 26.98% of the samples contained 17.76 ± 6.02 mg/cap of sibutramine. Daily therapeutic dose intake of sibutramine is in the range of 5 to 15 mg daily. Conclusion: Since apothecaries have advised consumers to take at least two capsules a day, it seems that the blood concentration of sibutramine will likely rise beyond the therapeutic concentration and become toxic. Therefore, the usage of such products could pose serious risks to consumers' health.


Assuntos
Depressores do Apetite , Perda de Peso , Contaminação de Medicamentos , Humanos , Irã (Geográfico) , Projetos Piloto
2.
Int J Clin Pharmacol Ther ; 59(8): 539-548, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34236303

RESUMO

OBJECTIVE: Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned. MATERIALS AND METHODS: In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months. RESULTS: 30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine. CONCLUSION: 30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.


Assuntos
Fármacos Antiobesidade , Depressores do Apetite , Adulto , Fármacos Antiobesidade/efeitos adversos , Humanos , México , Obesidade/tratamento farmacológico , Fentermina/efeitos adversos , Estudos Prospectivos
3.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R250-R259, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259025

RESUMO

The peptide hormone amylin reduces food intake and body weight and is an attractive candidate target for novel pharmacotherapies to treat obesity. However, the short half-life of native amylin and amylin analogs like pramlintide limits these compounds' potential utility in promoting sustained negative energy balance. Here, we evaluate the ability of the novel long-acting amylin/calcitonin receptor agonist ZP5461 to reduce feeding and body weight in rats, and also test the role of calcitonin receptors (CTRs) in the dorsal vagal complex (DVC) of the hindbrain in the energy balance effects of chronic ZP5461 administration. Acute dose-response studies indicate that systemic ZP5461 (0.5-3 nmol/kg) robustly suppresses energy intake and body weight gain in chow- and high-fat diet (HFD)-fed rats. When HFD-fed rats received chronic systemic administration of ZP5461 (1-2 nmol/kg), the compound initially produced reductions in energy intake and weight gain but failed to produce sustained suppression of intake and body weight. Using virally mediated knockdown of DVC CTRs, the ability of chronic systemic ZP5461 to promote early reductions in intake and body weight gain was determined to be mediated in part by activation of DVC CTRs, implicating the DVC as a central site of action for ZP5461. Future studies should address other dosing regimens of ZP5461 to determine whether an alternative dose/frequency of administration would produce more sustained body weight suppression.


Assuntos
Agonistas dos Receptores da Amilina/farmacologia , Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Receptores da Calcitonina/agonistas , Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/efeitos dos fármacos , Rombencéfalo/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Ingestão de Energia/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Receptores da Calcitonina/genética , Receptores da Calcitonina/metabolismo , Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/genética , Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/metabolismo , Rombencéfalo/metabolismo , Transdução de Sinais , Fatores de Tempo , Nervo Vago/metabolismo
4.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209507

RESUMO

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague-Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.


Assuntos
Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Endopeptidase Clp/farmacologia , Proteínas de Escherichia coli/farmacologia , Proteínas de Choque Térmico/farmacologia , Peptídeo YY/metabolismo , Animais , Anticorpos Antibacterianos/metabolismo , Western Blotting , Técnicas de Cultura de Células , Fragmentação do DNA , Ensaio de Imunoadsorção Enzimática , Escherichia coli/química , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley
5.
J Am Vet Med Assoc ; 259(1): 56-61, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34125612

RESUMO

OBJECTIVE: To determine whether IV propofol administration at a dose of 2 mg/kg (0.9 mg/lb) could induce food consumption by anorectic female dogs following elective ovariohysterectomy. ANIMALS: 51 healthy female dogs that failed to eat voluntarily when food was offered 6 hours after ovariohysterectomy. PROCEDURES: In a randomized, blinded, controlled clinical trial, dogs received propofol (2 mg/kg; n = 31) or an equivalent volume of saline (0.9% NaCl) solution (20) IV 6 hours after ovariohysterectomy. Afterward, food was offered to the dogs and food consumption was reassessed. Pain, sedation, and stress were scored before and immediately after treatment. RESULTS: 27 of the 31 (87%) dogs in the propofol group consumed food immediately after administration of the assigned treatment, whereas only 1 of 20 (5%) dogs in the placebo group did. No difference in pain, sedation, or stress scores was identified between the 2 groups. Sedation scores for dogs in the propofol group increased immediately after propofol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that food consumption following elective surgical procedures can be effectively induced in anorectic female dogs by IV administration of propofol at a dose of 2 mg/kg.


Assuntos
Depressores do Apetite , Doenças do Cão , Propofol , Animais , Cães , Feminino , Histerectomia/efeitos adversos , Histerectomia/veterinária , Ovariectomia/veterinária , Dor Pós-Operatória/veterinária , Propofol/efeitos adversos
6.
Eur J Pharmacol ; 901: 174072, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33823184

RESUMO

Glucagon-like peptide-2 (GLP-2) is secreted from enteroendocrine L-type cells of the gut and also released from preproglucagonergic (PPG) neurons in the nucleus tractus solitarius (NTS) and adjacent medial reticular nucleus of the brain stem. The neurons in the NTS express GLP-2, and the neurons send extensive projections to the hypothalamus. Recent studies show that the intracerebroventricular administration of GLP-2 significantly suppresses food intake in animals and some evidence suggest that the melanocortin receptor-4 (MC4-R) signaling in the hypothalamus is required for intracerebroventricular GLP-2-mediated inhibition of feeding. There is proopiomelanocortin (POMC) positive neurons expressing MC4-R in the NTS. Suppression of MC4-R expressing neurons in the brain stem inhibits gastric emptying. In this study, we tested the effects of NTS GLP-2R activation and blockade on feeding behavior and evaluated the endogenous melanocortin system's role in the NTS in mediating effects of GLP-2 on feeding behavior in fed and fasted rats. Our results demonstrated that microinjection of GLP-2 into the NTS suppressed food intake in fasted-refeeding rats but did not affect food intake in free-feeding rats, and this inhibition was blocked by pretreatment of either Exendin (9-39) or SHU 9119, suggesting the GLP-2 system in the NTS exerts an inhibitory action on food intake. MC4-R mediates this action in the NTS.


Assuntos
Depressores do Apetite/farmacologia , Peptídeo 2 Semelhante ao Glucagon/farmacologia , Receptor Tipo 4 de Melanocortina/efeitos dos fármacos , Núcleo Solitário , Animais , Ingestão de Alimentos/efeitos dos fármacos , Jejum , Peptídeo 2 Semelhante ao Glucagon/administração & dosagem , Peptídeo 2 Semelhante ao Glucagon/antagonistas & inibidores , Masculino , Hormônios Estimuladores de Melanócitos/farmacologia , Microinjeções , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley
7.
Sci Rep ; 11(1): 6791, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762661

RESUMO

To examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. A double-blind, randomised, placebo controlled trial to examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. Eighty-three men and women aged between 20 and 50 years of age completed 16 weeks of daily supplementation with either CFE or placebo. Plasma cardiometabolic (lipid profile, glucose, insulin) and satiety (ghrelin, leptin, neuropeptideY) biomarkers, body composition, diet history and gastrointenstinal function were assessed at baseline, weeks 4, 8, 12 and 16. Subjects in the CFE and placebo groups were well matched and predominatly female 93% and 87.5%, with a mean age of 40.9 ± 6.7 and 39.5 ± 7.5 years and body mass index (BMI) of 30.0 ± 3.1 and 30.2 ± 2.9 kg/m2 respectively. There was a significant difference in plasma leptin concentration change between groups at week 16 (p = 0.04), with the placebo group increasing concentration (2.27 ± 4.80 ng/mL) while the CFE group (0.05 ± 4.69 ng/mL) remained the same. At week 16, the CFE group had significantly reduced their calorie intake from baseline compared to the placebo group (245 cal vs 15.8 cal respectively p < 0.01). The CFE group also had a significant reduction in waist circumference of 2.7 cm compared to an increase of 0.3 cm in the placebo group (p = 0.02). A weight increase from baseline was seen in the placebo group that was not observed in the CFE group (1.33 kg weight gain vs 0.37 kg weight loss respectively; p = 0.03). The placebo group also had a significant increase in fat mass, android fat mass, BMI and leptin compared to the CFE group (p = 0.04, 0.02, < 0.01 respectively). CFE was effective at maintaining bodyweight during a non-calorie controlled diet compared to a placebo. The mechanism responsible for this action is requiring further research and could be due to an increase in satiety receptor sensitivity.


Assuntos
Apocynaceae/química , Depressores do Apetite/uso terapêutico , Regulação do Apetite/efeitos dos fármacos , Sobrepeso/dietoterapia , Extratos Vegetais/farmacologia , Administração Oral , Adulto , Apocynaceae/metabolismo , Depressores do Apetite/química , Depressores do Apetite/farmacologia , Biomarcadores/sangue , Índice de Massa Corporal , Método Duplo-Cego , Ingestão de Energia/efeitos dos fármacos , Humanos , Leptina/sangue , Pessoa de Meia-Idade , Sobrepeso/patologia , Efeito Placebo , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Circunferência da Cintura/efeitos dos fármacos , Adulto Jovem
8.
Cochrane Database Syst Rev ; 3: CD012650, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765343

RESUMO

BACKGROUND: Clinicians primarily recommend weight loss for obese women seeking pregnancy. The effectiveness of interventions aimed at weight loss in obese women with subfertility is unclear. OBJECTIVES: To assess the effectiveness and safety of pharmacological and non-pharmacological strategies compared with each other, placebo, or no treatment for achieving weight loss in obese women with subfertility. SEARCH METHODS: We searched the CGF Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and AMED from inception to 18 August 2020. We also checked reference lists and contacted experts in the field for additional relevant papers. SELECTION CRITERIA: We included published and unpublished randomised controlled trials in which weight loss was the main goal of the intervention. Our primary effectiveness outcomes were live birth or ongoing pregnancy and primary safety outcomes were miscarriage and adverse events. Secondary outcomes included clinical pregnancy, weight change, quality of life, and mental health outcome. DATA COLLECTION AND ANALYSIS: Review authors followed standard Cochrane methodology. MAIN RESULTS: This review includes 10 trials. Evidence was of very low to low quality: the main limitations were due to lack of studies and poor reporting of study methods. The main reasons for downgrading evidence were lack of details by which to judge risk of bias (randomisation and allocation concealment), lack of blinding, and imprecision. Non-pharmacological intervention versus no intervention or placebo Evidence is insufficient to determine whether a diet or lifestyle intervention compared to no intervention affects live birth (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.65 to 1.11; 918 women, 3 studies; I² = 78%; low-quality evidence). This suggests that if the chance of live birth following no intervention is assumed to be 43%, the chance following diet or lifestyle changes would be 33% to 46%. We are uncertain if lifestyle change compared with no intervention affects miscarriage rate (OR 1.54, 95% CI 0.99 to 2.39; 917 women, 3 studies; I² = 0%; very low-quality evidence). Evidence is insufficient to determine whether lifestyle change compared with no intervention affects clinical pregnancy (OR 1.06, 95% CI 0.81 to 1.40; 917 women, 3 studies; I² = 73%; low-quality evidence). Lifestyle intervention resulted in a decrease in body mass index (BMI), but data were not pooled due to heterogeneity in effect (mean difference (MD) -3.70, 95% CI -4.10 to -3.30; 305 women, 1 study; low-quality evidence; and MD -1.80, 95% CI -2.67 to -0.93; 43 women, 1 study; very low-quality evidence). Non-pharmacological versus non-pharmacological intervention We are uncertain whether intensive weight loss interventions compared to standard care nutrition counselling affects live birth (OR 11.00, 95% CI 0.43 to 284; 11 women, 1 study; very low-quality evidence), clinical pregnancy (OR 11.00, 95% CI 0.43 to 284; 11 women, 1 study; very low-quality evidence), BMI (MD -3.00, 95% CI -5.37 to -0.63; 11 women, 1 study; very low-quality evidence), weight change (MD -9.00, 95% CI -15.50 to -2.50; 11 women, 1 study; very low-quality evidence), quality of life (MD 0.06, 95% CI -0.03 to 0.15; 11 women, 1 study; very low-quality evidence), or mental health (MD -7.00, 95% CI -13.92 to -0.08; 11 women, 1 study; very low-quality evidence). No study reported on adverse events . Pharmacological versus pharmacological intervention For metformin plus liraglutide compared to metformin we are uncertain of an effect on the adverse events nausea (OR 7.22, 95% CI 0.72 to 72.7; 28 women, 1 study; very low-quality evidence), diarrhoea (OR 0.31, 95% CI 0.01 to 8.3; 28 women, 1 study; very low-quality evidence), and headache (OR 5.80, 95% CI 0.25 to 133; 28 women, 1 study; very low-quality evidence). We are uncertain if a combination of metformin plus liraglutide vs metformin affects BMI (MD 2.1, 95% CI -0.42 to 2.62; 28 women, 1 study; very low-quality evidence) and total body fat (MD -0.50, 95% CI -4.65 to 3.65; 28 women, 1 study; very low-quality evidence). For metformin, clomiphene, and L-carnitine versus metformin, clomiphene, and placebo, we are uncertain of an effect on miscarriage (OR 3.58, 95% CI 0.73 to 17.55; 274 women, 1 study; very low-quality evidence), clinical pregnancy (OR 5.56, 95% CI 2.57 to 12.02; 274 women, 1 study; very low-quality evidence) or BMI (MD -0.3, 95% CI 1.17 to 0.57, 274 women, 1 study, very low-quality evidence). We are uncertain if dexfenfluramine versus placebo affects weight loss in kilograms (MD -0.10, 95% CI -2.77 to 2.57; 21 women, 1 study; very low-quality evidence). No study reported on live birth, quality of life, or mental health outcomes. Pharmacological intervention versus no intervention or placebo We are uncertain if metformin compared with placebo affects live birth (OR 1.57, 95% CI 0.44 to 5.57; 65 women, 1 study; very low-quality evidence). This suggests that if the chance of live birth following placebo is assumed to be 15%, the chance following metformin would be 7% to 50%. We are uncertain if metformin compared with placebo affects gastrointestinal adverse events (OR 0.91, 95% CI 0.32 to 2.57; 65 women, 1 study; very low-quality evidence) or miscarriage (OR 0.50, 95% CI 0.04 to 5.80; 65 women, 1 study; very low-quality evidence) or clinical pregnancy (OR 2.67, 95% CI 0.90 to 7.93; 96 women, 2 studies; I² = 48%; very low-quality evidence). We are also uncertain if diet combined with metformin versus diet and placebo affects BMI (MD -0.30, 95% CI -2.16 to 1.56; 143 women, 1 study; very low-quality evidence) or waist-to-hip ratio (WHR) (MD 2.00, 95% CI -2.21 to 6.21; 143 women, 1 study; very low-quality evidence). Pharmacological versus non-pharmacological intervention No study undertook this comparison. AUTHORS' CONCLUSIONS: Evidence is insufficient to support the use of pharmacological and non-pharmacological strategies for obese women with subfertility. No data are available for the comparison of pharmacological versus non-pharmacological strategies. We are uncertain whether pharmacological or non-pharmacological strategies effect live birth, ongoing pregnancy, adverse events, clinical pregnancy, quality of life, or mental heath outcomes. However, for obese women with subfertility, a lifestyle intervention may reduce BMI. Future studies should compare a combination of pharmacological and lifestyle interventions for obese women with subfertility.


Assuntos
Infertilidade Feminina/terapia , Nascido Vivo/epidemiologia , Obesidade/terapia , Perda de Peso , Aborto Espontâneo/epidemiologia , Depressores do Apetite/uso terapêutico , Viés , Carnitina/uso terapêutico , Clomifeno/uso terapêutico , Dexfenfluramina/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Infertilidade Feminina/dietoterapia , Estilo de Vida , Liraglutida/efeitos adversos , Liraglutida/uso terapêutico , Saúde Mental , Metformina/efeitos adversos , Metformina/uso terapêutico , Obesidade/dietoterapia , Gravidez , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Cochrane Database Syst Rev ; 1: CD007654, 2021 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-33454957

RESUMO

BACKGROUND: This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect. OBJECTIVES: Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work. SELECTION CRITERIA: Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity. MAIN RESULTS: This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension. AUTHORS' CONCLUSIONS: In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Depressores do Apetite/efeitos adversos , Hipertensão/tratamento farmacológico , Adulto , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Viés , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Dieta Redutora , Combinação de Medicamentos , Feminino , Frutose/efeitos adversos , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Hipertensão/mortalidade , Lactonas/efeitos adversos , Lactonas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Orlistate/efeitos adversos , Orlistate/uso terapêutico , Fentermina/efeitos adversos , Fentermina/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Retirada de Medicamento Baseada em Segurança , Tempo , Topiramato/efeitos adversos , Topiramato/uso terapêutico
10.
Mini Rev Med Chem ; 21(6): 724-730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33245271

RESUMO

Fenugreek (Trigonella foenum-graecum L.) is a native plant found in the parts of Iran to the North of India, and is presently planted also in other regions of the world. Fenugreek is considered a notable multipurpose medicinal and traditional herb in Iran, India, and China for several centuries. The most important components of fenugreek seeds are protein, neutral detergent fiber, gum, lipids, moisture, ash and starch. Fenugreek seeds and leaves are anti-cholesterolemic, anti-tumor, antiinflammatory, carminative, demulcent, deobstruent, emollient, expectorant, galactogogue, febrifuge, laxative, hypoglycaemic, restorative, parasiticide and uterine tonic and useful in burning sensation. Traditionally, fenugreek seeds being used worldwide are beneficial for bone and muscles, respiratory system, gastro-intestinal system, female reproductive system, cardio-vascular system, endocrinology and hepatic. Fenugreek helps reduce cholesterol, reduce cardiovascular risk, control diabetes, a good consolation for sore throats, a remedy for acid reflux, constipation, colon cancer prevention, appropriate for kidney trouble, skin infection, increase milk production, reduce menstrual discomfort, and reduce menopause symptoms. It is also an appetite suppressant that helps in weight loss. Both modern science and traditional medicine integration with novel technologies and discoveries will secure the cultivation of medicinal herbs and promote sustainability in the long-term and a wide-range.


Assuntos
Medicina Tradicional/história , Extratos Vegetais/química , Trigonella/química , Depressores do Apetite/química , Depressores do Apetite/isolamento & purificação , Depressores do Apetite/farmacologia , Doenças Cardiovasculares/prevenção & controle , História Antiga , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Sementes/química , Sementes/metabolismo , Trigonella/metabolismo , Perda de Peso/efeitos dos fármacos
11.
Am J Physiol Regul Integr Comp Physiol ; 320(3): R236-R249, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33206556

RESUMO

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp's ability to reduce food intake and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacological dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food intake and water intake. Blockade of Gpr160 in the 4V, independent of pharmacological CART treatment, caused an increase in both overnight food intake and water intake. The decrease in food intake, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a glucagon-like peptide 1 (GLP-1) receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and nonneuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection and extend these findings to water drinking. Gpr160ir was observed in both neuronal and nonneuronal cell types in regions known to be important in the multiple pharmacological effects of CARTp, identifying those areas as targets for future compromise of function studies.


Assuntos
Depressores do Apetite/farmacologia , Tronco Encefálico/efeitos dos fármacos , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Proteínas do Tecido Nervoso/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Animais , Tronco Encefálico/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Masculino , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo
12.
Acta Pharm ; 71(2): 279-291, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151165

RESUMO

The current study investigates the anorectic interaction and safety of the mazindol-metformin combination in rats. Isobologram and interaction index were used to determine anorectic interaction between mazindol and metformin in the sweetened milk model. The safety profile of the mazindol-metformin combination was determined by measuring anxiety, blood pressure, hematic biometry and blood chemistry. An acute dose of mazindol and metformin administered per os, individually or as a mixture, has reduced the milk consumption in rats in a dose-dependent manner. Theoretical effective dose 40 (ED40t) did not differ from the experimental effective dose 40 (ED40e) obtained with the mazindol-metformin mixture in the anorexia experiments, by Student's t-test. In addition, the interaction index confirmed the additive anorectic effect between both drugs. A single oral dose of ED40e mazindol-metformin mixture induced anxiolysis in the elevated plus-maze test. Moreover, oral administration of mazindol-metformin combination for 3 months significantly decreased glycemia, but not blood pressure nor other parameters of hematic biometry and blood chemistry. Results suggest that mazindol-metformin combination exerts an additive anorectic effect, as well as anxiolytic and hypoglycemic properties. Mazindol-metformin combination might be useful in obese patients with anxiety disorders or diabetes risk factors.


Assuntos
Depressores do Apetite/farmacologia , Mazindol/farmacologia , Metformina/farmacologia , Administração Oral , Animais , Depressores do Apetite/administração & dosagem , Depressores do Apetite/toxicidade , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Hipoglicemiantes/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Mazindol/administração & dosagem , Mazindol/toxicidade , Metformina/administração & dosagem , Metformina/toxicidade , Ratos , Ratos Wistar
13.
Pathologica ; 113(6): 475-480, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34974555

RESUMO

Rectal prolapse is a disorder in which the rectum protrudes from the anal canal. Solitary rectal ulcer may coexist. Both conditions have been associated with chronic constipation and excessive straining during defecation. Rectal prolapse has been rarely reported in women suffering from anorexia nervosa. Lack of rectal support because of loss of ischiorectal fat has been proposed as one of the possible mechanisms in this condition, together with chronic constipation and abuse of laxative. We report the case of an anorexic woman with a severe rectal prolapse and bleeding requiring urgent Altmeier's procedure. Surgery was complicated by dehiscence of the anastomosis and volvulus, requiring ileostomy and laciniae debridement. Pathological analysis of all the surgical samples taken from different abdominal sites highlighted changes in the visceral adipose tissue consisting in nodular aggregates of small adipocytes dispersed in a myxoid matrix surrounding blood vessels within abundant fibrosis. The morphologic features resemble those observed in primordial fetal fat and are comparable to those observed in cancer associated cachexia. The diffuse myxoid degeneration of visceral adipose tissue may play a role in the pathogenesis of rectal prolapse in patients with anorexia nervosa. Besides starvation, the mechanism sustaining myxoid degeneration of the adipose tissue is not entirely clear. Whenever possible improving nutritional and clinical conditions should be ideal before any surgical approach.


Assuntos
Depressores do Apetite , Doenças Retais , Prolapso Retal , Feminino , Humanos , Gordura Intra-Abdominal , Prolapso Retal/complicações , Prolapso Retal/cirurgia , Úlcera
14.
PLoS One ; 15(12): e0244793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382813

RESUMO

Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been limited. Recently, we have identified two partially redundant enhancers, nPE1 and nPE2, that drive proopiomelanocortin gene expression in the hypothalamus. Here we demonstrate that deletion of nPE1 produces mild obesity while knockout of nPE2 has no discernible metabolic phenotypes. Additionally, we show that acute leptin administration has significant effects on nPE1 knockout mice, with food intake and body weight change significantly impacted by peripheral leptin treatment. nPE1 knockout mice became less responsive to leptin treatment over time as percent body weight change increased over 2 week exposure to peripheral leptin. Both Pomc and Agrp mRNA were not differentially affected by chronic leptin treatment however we did see a decrease in Pomc and Agrp mRNA in both nPE1 and nPE2 knockout calorie restricted mice as compared to calorie restricted PBS-treated WT mice. Collectively, these data suggest dynamic regulation of Pomc by nPE1 such that mice with nPE1 knockout become less responsive to the anorectic effects of leptin treatment over time. Our results also support our earlier findings in which nPE2 may only be critical in adult mice that lack nPE1, indicating that these neural enhancers work synergistically to influence metabolism.


Assuntos
Depressores do Apetite/farmacologia , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Elementos Facilitadores Genéticos , Hipotálamo/efeitos dos fármacos , Leptina/farmacologia , Neurônios/efeitos dos fármacos , Pró-Opiomelanocortina/genética , Animais , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo
15.
Nutrients ; 12(11)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138061

RESUMO

Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of 9 h. Fifteen younger (27 ± 1 years, 25.8 ± 0.7 kg/m2) and 15 older (75 ± 2 years, 26.6 ± 0.8 kg/m2) healthy men were studied on three occasions on which they received, in a randomized order, a 30 g/120 kcal, 70 g/280 kcal whey-protein, or control (~2 kcal) drink. Ad-libitum energy intake (sum of breakfast, lunch, and dinner) was suppressed in a protein load responsive fashion (P = 0.001). Suppression was minimal at breakfast, substantial at lunch (~-16%, P = 0.001), no longer present by dinner, and was less in older than younger men (-3 ± 4% vs. -8 ± 4%, P = 0.027). Cumulative protein intake was increased in the younger and older men (+20% and +42%, P < 0.001). Visual analogue scale ratings of fullness were higher and desire to eat and prospective food consumption were lower after protein vs. control, and these effects were smaller in older vs. younger men (interaction effect P < 0.05). These findings support the use of whey-protein drink supplements in older people who aim to increase their protein intake without decreasing their overall energy intake.


Assuntos
Fatores Etários , Apetite/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Refeições/efeitos dos fármacos , Proteínas do Soro do Leite/administração & dosagem , Adulto , Idoso , Depressores do Apetite/administração & dosagem , Bebidas , Desjejum/efeitos dos fármacos , Suplementos Nutricionais , Voluntários Saudáveis , Humanos , Almoço/efeitos dos fármacos , Masculino , Fatores de Tempo
17.
Am J Physiol Regul Integr Comp Physiol ; 319(6): R673-R683, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026822

RESUMO

Oxytocin (OT) is a neuropeptide whose central receptor-mediated actions include reducing food intake. One mechanism of its behavioral action is the amplification of the feeding inhibitory effects of gastrointestinal (GI) satiation signals processed by hindbrain neurons. OT treatment also reduces carbohydrate intake in humans and rodents, and correspondingly, deficits in central OT receptor (OT-R) signaling increase sucrose self-administration. This suggests that additional processes contribute to central OT effects on feeding. This study investigated the hypothesis that central OT reduces food intake by decreasing food seeking and food motivation. As central OT-Rs are expressed widely, a related focus was to assess the role of one or more OT-R-expressing nuclei in food motivation and food-seeking behavior. OT was delivered to the lateral ventricle (LV), nucleus tractus solitarius (NTS), or ventral tegmental area (VTA), and a progressive ratio (PR) schedule of operant reinforcement and an operant reinstatement paradigm were used to measure motivated feeding behavior and food-seeking behavior, respectively. OT delivered to the LV, NTS, or VTA reduced 1) motivation to work for food and 2) reinstatement of food-seeking behavior. Results provide a novel and additional interpretation for central OT-driven food intake inhibition to include the reduction of food motivation and food seeking.


Assuntos
Depressores do Apetite/administração & dosagem , Regulação do Apetite/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Ventrículos Laterais/efeitos dos fármacos , Motivação/efeitos dos fármacos , Ocitocina/administração & dosagem , Núcleo Solitário/efeitos dos fármacos , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Infusões Intraventriculares , Ventrículos Laterais/fisiologia , Masculino , Ratos Sprague-Dawley , Núcleo Solitário/fisiologia , Área Tegmentar Ventral/fisiologia
18.
Anal Bioanal Chem ; 412(29): 8135-8144, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32914397

RESUMO

Immunochromatographic assay (ICA) has been used widely for the onsite monitoring of illegal additives due to its simplicity, speed, and low cost. However, a scanner is commonly required for ICA to achieve quantitative results. In this work, we developed a visual semi-quantitative ICA for sibutramine, a banned additive in diet foods, without the need for a scanner for measurement. Monoclonal antibodies specific for sibutramine were raised and conjugated with upconversion nanoparticles (UCNPs) as the luminescent tracer. ICA was developed by employing multiple test lines to achieve the semi-quantitative detection of sibutramine. Based on the optimal conditions, the cutoff levels (limit of quantitation, LOQ) of T1 line, T2 line, T3 line, and T4 line were 0.02 µg/mL, 0.15 µg/mL, 1.0 µg/mL, and 7.5 µg/mL, respectively, in buffer system. The ICA demonstrated a LOQ at 0.2 mg/kg for sibutramine in diet food samples. The assay (including pretreatment) can be finished within 30 min without the aid of other instruments, except a laser pen. No false positive or false negative results were observed. The results indicated that the proposed method was reliable, simple, and rapid for the screening of sibutramine abuse in diet food samples.


Assuntos
Depressores do Apetite/análise , Cromatografia de Afinidade/métodos , Ciclobutanos/análise , Nanopartículas/química , Animais , Anticorpos Monoclonais/química , Ensaio de Imunoadsorção Enzimática , Contaminação de Alimentos/análise , Limite de Detecção , Camundongos , Espectrometria de Fluorescência
19.
J Nutr Biochem ; 85: 108456, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32810797

RESUMO

Obesity is critically related with the development of metabolic and pathophysiological alterations among which non-alcoholic fatty liver disease (NAFLD) is of especial relevance. Although there are numerous strategies to successfully treat obesity, the prevention of weight regain still remains challenging for individuals who have undergone weight loss programs. In such context, diet and physical activity are considered essential for the regulation of body weight and lipid metabolism. In this study, rats were fed a high-fat diet (HFD) to induce obesity and alterations in hepatic lipid metabolism. Obese rats were then treated with single or combined strategies of caloric restriction, physical exercise, and/or pharmacological treatment with an appetite suppressant, to lose weight, reverse the obesity-related alterations in hepatic morphology and lipid metabolism and maintain the beneficial effects of the interventions used. HFD induced excess body weight, hepatic steatosis, altered fatty acid profile, dysregulated gene expression of lipogenic and lipolytic enzymes, as well as plasma markers of liver damage, and modifications in liver antioxidant enzyme activity. Such alterations were ameliorated by caloric restriction in combination with a mixed training protocol and/or food-intake inhibitor administration during a weight loss intervention period of 3 weeks, and the beneficial effects remained after 6 weeks of weight maintenance, with some interesting interactions observed. In conclusion, weight loss strategies assayed were efficient at correcting the obesogenic action of a HFD and related alterations in hepatic functionality through different molecular mechanisms. The beneficial effects were also evident along the post-intervention maintenance period to avoid body weight regain.


Assuntos
Depressores do Apetite/uso terapêutico , Manutenção do Peso Corporal , Restrição Calórica , Terapia por Exercício , Fígado/metabolismo , Obesidade/terapia , Animais , Manutenção do Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Obesidade/metabolismo , Ratos Sprague-Dawley , Perda de Peso/efeitos dos fármacos
20.
Peptides ; 132: 170366, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32634450

RESUMO

Amylin is a peptide hormone that is mainly known to be produced by pancreatic ß-cells in response to a meal but amylin is also produced by brain cells in discrete brain areas albeit in a lesser amount. Amylin receptor (AMY) is composed of the calcitonin core-receptor (CTR) and one of the 3 receptor activity modifying protein (RAMP), thus forming AMY1-3; RAMP enhances amylin binding properties to the CTR. However, amylin receptor agonist such as salmon calcitonin is able to bind CTR alone. Peripheral amylin's main binding site is located in the area postrema (AP) which then propagate the signal to the nucleus of the solitary tract and lateral parabrachial nucleus (LPBN) and it is then transmitted to the forebrain areas such as central amygdala and bed nucleus of the stria terminalis. Amylin's activation of these different brain areas mediates eating and other metabolic pathways controlling energy expenditure and glucose homeostasis. Peripheral amylin can also bind in the arcuate nucleus of the hypothalamus where it acts independently of the AP to activate POMC and NPY neurons. Amylin activation of NPY neurons has been shown to be transmitted to LPBN neurons to act on eating while amylin POMC signaling affects energy expenditure and locomotor activity. While a large amount of experiments have already been conducted, future studies will have to further investigate how amylin is taken up by forebrain areas and deepen our understanding of amylin action on peripheral metabolism.


Assuntos
Depressores do Apetite/metabolismo , Encéfalo/metabolismo , Ingestão de Alimentos/fisiologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Animais , Humanos , Hormônios Pancreáticos/metabolismo , Transdução de Sinais
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