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1.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R917-R928, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32208925

RESUMO

Phoenixin is a 20-amino acid peptide (PNX-20) cleaved from the small integral membrane protein 20 (SMIM20), with multiple biological roles in mammals. However, its role in nonmammalian vertebrates is poorly understood. This research aimed to determine whether PNX-20 influences feeding and metabolism in zebrafish. The mRNAs encoding SMIM20 and its putative receptor, super conserved receptor expressed in brain 3 (SREB3), are present in both central and peripheral tissues of zebrafish. Immunohistochemical analysis confirmed the presence of PNX-like immunoreactivity in the gut and in zebrafish liver (ZFL) cell line. We also found that short-term fasting (7 days) significantly decreased smim20 mRNA expression in the brain, gut, liver, gonads, and muscle, which suggests a role for PNX-20 in food intake regulation. Indeed, single intraperitoneal injection of 1,000 ng/g body wt PNX-20 reduced feeding in both male and female zebrafish, likely in part by enhancing hypothalamic cart and reducing hypothalamic/gut preproghrelin mRNAs. Furthermore, the present results demonstrated that PNX-20 modulates the expression of genes involved in glucose transport and metabolism in ZFL cells. In general terms, such PNX-induced modulation of gene expression was characterized by the upregulation of glycolytic genes and the downregulation of gluconeogenic genes. A kinetic study of the ATP production rate from both glycolytic and mitochondrial pathways demonstrated that PNX-20-treated ZFL cells exhibited significantly higher ATP production rate associated with glycolysis than control cells. This confirms a positive role for PNX-20 on glycolysis. Together, these results indicate that PNX-20 is an anorexigen with important metabolic roles in zebrafish.


Assuntos
Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Proteínas de Homeodomínio/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas de Peixe-Zebra/farmacologia , Peixe-Zebra/metabolismo , Animais , Regulação do Apetite/efeitos dos fármacos , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Glicólise/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Transdução de Sinais , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
2.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
3.
PLoS Biol ; 18(2): e3000629, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32097406

RESUMO

Human biology has evolved to keep body fat within a range that supports survival. During the last 25 years, obesity biologists have uncovered key aspects of physiology that prevent fat mass from becoming too low. In contrast, the mechanisms that counteract excessive adipose expansion are largely unknown. Evidence dating back to the 1950s suggests the existence of a blood-borne molecule that defends against weight gain. In this article, we discuss the research supporting an "unidentified factor of overfeeding" and models that explain its role in body weight control. If it exists, revealing the identity of this factor could end a long-lasting enigma of energy balance regulation and facilitate a much-needed breakthrough in the pharmacological treatment of obesity.


Assuntos
Depressores do Apetite/metabolismo , Peso Corporal/fisiologia , Hormônios/metabolismo , Tecido Adiposo/metabolismo , Animais , Depressores do Apetite/sangue , Hormônios/sangue , Humanos , Hiperfagia/genética , Hiperfagia/metabolismo , Obesidade/genética , Obesidade/metabolismo , Parabiose , Ganho de Peso/fisiologia
4.
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
5.
Am J Public Health ; 110(1): 109-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751147

RESUMO

Objectives. To investigate the prospective association of diet pill and laxative use for weight control with subsequent first eating disorder diagnosis in young women.Methods. We used longitudinal data from 10 058 US women spanning 2001 through 2016. We used multivariable logistic regression models, adjusting for age, race/ethnicity, and overweight status to estimate the association between weight-control behaviors and subsequent eating disorder diagnosis.Results. Among those who had not previously received an eating disorder diagnosis, women who reported diet pill (adjusted odds ratio [AOR] = 5.6; 95% confidence interval [CI] = 3.0, 10.5) or laxative (AOR = 6.0; 95% CI = 4.2, 8.7) use for weight control had higher odds of receiving a subsequent first eating disorder diagnosis within 1 to 3 years than those who did not report using these products.Conclusions. Use of diet pills or laxatives for weight loss can be dangerous and may be a warning sign that warrants counseling and evaluation for the presence of or risk of developing an eating disorder.Public Health Implications. Policymakers and public health professionals should develop and evaluate policy initiatives to reduce or prohibit access to diet pills and laxatives abused for weight control.


Assuntos
Depressores do Apetite/administração & dosagem , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Laxantes/administração & dosagem , Perda de Peso , Adolescente , Adulto , Uso de Medicamentos , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Razão de Chances , Estudos Prospectivos , Estados Unidos/epidemiologia , Adulto Jovem
6.
J Med Chem ; 63(1): 382-390, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31850759

RESUMO

The effects of oxytocin on food intake and body weight reduction have been demonstrated in both animal models and human clinical studies. Despite being efficacious, oxytocin is enzymatically unstable and thus considered to be unsuitable for long-term use in patients with obesity. Herein, a series of oxytocin derivatives were engineered through conjugation with fatty acid moieties that are known to exhibit high binding affinities to serum albumin. One analog (OT-12) in particular was shown to be a potent full agonist at the oxytocin receptor (OTR) in vitro with good selectivity and long half-life (24 h) in mice. Furthermore, OT-12 is peripherally restricted, with very limited brain exposure (1/190 of the plasma level). In a diet-induced obesity mouse model, daily subcutaneous administration of OT-12 exhibited more potent anorexigenic and body weight reducing effects than carbetocin. Thus, our results suggest that the long-acting, peripherally restricted OTR agonist may offer potential therapeutic benefits for obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Lipopeptídeos/uso terapêutico , Ocitocina/análogos & derivados , Ocitocina/uso terapêutico , Receptores de Ocitocina/agonistas , Animais , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/farmacocinética , Depressores do Apetite/síntese química , Depressores do Apetite/farmacocinética , Peso Corporal/efeitos dos fármacos , Humanos , Lipopeptídeos/síntese química , Lipopeptídeos/farmacocinética , Masculino , Camundongos Endogâmicos BALB C , Obesidade/tratamento farmacológico , Ocitocina/farmacocinética , Engenharia de Proteínas , Perda de Peso/efeitos dos fármacos
7.
PLoS Biol ; 17(12): e3000482, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805040

RESUMO

Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of peptide YY3-36 (PYY3-36), lithium chloride, glucagon-like peptide 1 (GLP-1), and leptin shows the precise behavioural changes caused by each anorectic agent. Our analysis demonstrates that the changes in feeding behaviour evoked by the anorectic agents investigated do not mimic the behaviour of well-fed animals and that the intermeal interval is influenced by fullness. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating upper gut emptying can be as effective as anorectic drug administration.


Assuntos
Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Animais , Depressores do Apetite/farmacologia , Ingestão de Alimentos/fisiologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Homeostase/efeitos dos fármacos , Leptina/farmacologia , Masculino , Camundongos , Obesidade , Fragmentos de Peptídeos/farmacologia , Peptídeo YY/farmacologia , Ratos
8.
Int J Mol Sci ; 20(20)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615150

RESUMO

The micronutrients vitamins B9 and B12 act as methyl donors in the one-carbon metabolism involved in transmethylation reactions which critically influence epigenetic mechanisms and gene expression. Both vitamins are essential for proper development, and their deficiency during pregnancy has been associated with a wide range of disorders, including persisting growth retardation. Energy homeostasis and feeding are centrally regulated by the hypothalamus which integrates peripheral signals and acts through several orexigenic and anorexigenic mediators. We studied this regulating system in a rat model of methyl donor deficiency during gestation and lactation. At weaning, a predominance of the anorexigenic pathway was observed in deficient pups, with increased plasma peptide YY and increased hypothalamic pro-opiomelanocortin (POMC) mRNA, in line with abnormal leptin, ghrelin, and insulin secretion and/or signaling during critical periods of fetal and/or postnatal development of the hypothalamus. These results suggest that early methyl donor deficiency can affect the development and function of energy balance circuits, resulting in growth and weight deficits. Maternal administration of folic acid (3 mg/kg/day) during the perinatal period tended to rectify peripheral metabolic signaling and central neuropeptide and receptor expression, leading to reduced growth retardation.


Assuntos
Metabolismo Energético/genética , Grelina/genética , Peptídeo YY/genética , Pró-Opiomelanocortina/genética , Animais , Depressores do Apetite/farmacologia , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Ácido Fólico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Grelina/sangue , Hipotálamo/metabolismo , Insulina/sangue , Insulina/genética , Lactação , Leptina/sangue , Leptina/genética , Metilação/efeitos dos fármacos , Peptídeo YY/sangue , Gravidez , Pró-Opiomelanocortina/sangue , RNA Mensageiro/genética , Ratos , Vitamina B 12/genética , Vitamina B 12/farmacologia
9.
Nutrients ; 11(9)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533291

RESUMO

The prevalence of obesity is increasing worldwide. Bioactive phytochemicals in food supplements are a trending approach to facilitate dieting and to improve patients' adherence to reducing food and caloric intake. The aim of this systematic review was to assess efficacy and safety of the most commonly used bioactive phytochemicals with appetite/hunger-suppressing and/or satiety/fullness-increasing properties. To be eligible, studies needed to have included at least 10 patients per group aged 18 years or older with no serious health problems except for overweight or obesity. Of those studies, 32 met the inclusion criteria, in which 27 different plants were tested alone or as a combination, regarding their efficacy in suppressing appetite/hunger and/or increasing satiety/fullness. The plant extracts most tested were derived from Camellia sinensis (green tea), Capsicum annuum, and Coffea species. None of the plant extracts tested in several trials showed a consistent positive treatment effect. Furthermore, only a few adverse events were reported, but none serious. The findings revealed mostly inconclusive evidence that the tested bioactive phytochemicals are effective in suppressing appetite/hunger and/or increasing satiety/fullness. More systematic and high quality clinical studies are necessary to determine the benefits and safety of phytochemical complementary remedies for dampening the feeling of hunger during dieting.


Assuntos
Depressores do Apetite/uso terapêutico , Regulação do Apetite/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Obesidade/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Resposta de Saciedade/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/psicologia , Compostos Fitoquímicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Obesity (Silver Spring) ; 27(11): 1874-1882, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31562706

RESUMO

OBJECTIVE: Amphetamine was formerly used as a treatment to combat obesity, but amphetamine's use as an appetite suppressant was discontinued because of its significant abuse potential. Most of the rewarding and reinforcing effects of amphetamine differ by sex, with females showing higher levels of drug intake and amphetamine-induced motivation, relapse, and locomotion, but it is unknown whether amphetamine's effects on feeding also differ by sex. Furthermore, previous research on the anorectic effects of amphetamine has been focused primarily on its effects on baseline homeostatic feeding, but it is unknown whether amphetamine also affects hedonic, reward-related feeding, which is an important factor driving the rise in obesity levels. METHODS: This study tested whether amphetamine alters food intake in a sex-dependent manner in two reward-related feeding paradigms: a sucrose two-bottle choice test and a high-fat/high-sugar binge intake model. RESULTS: Amphetamine altered food intake equally in males and females in both paradigms, with higher doses significantly inhibiting feeding and low doses of amphetamine increasing feeding at later time points. CONCLUSIONS: Amphetamine's effects on feeding and drug reward may be mediated by distinct mechanisms, which could allow for the development of new approaches to combat obesity with limited abuse and addiction-related side effects.


Assuntos
Anfetamina/farmacologia , Bulimia , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ingestão de Energia/efeitos dos fármacos , Sacarose/administração & dosagem , Animais , Depressores do Apetite/farmacologia , Bulimia/induzido quimicamente , Bulimia/metabolismo , Bulimia/prevenção & controle , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores Sexuais
11.
Expert Opin Pharmacother ; 20(16): 1981-1991, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31487204

RESUMO

Introduction: Obstructive sleep apneas are a frequent clinical condition in which there are momentary interruptions or reductions in breathing activity. To date, the gold standard therapy is the use of Continous Positive Airway Pressure (CPAP). But, due to the relatevely high frequency of poor compliant patients, there is the need to research possible pharmacological treatments for obstructive apnea (OSA). Areas covered: A recent study divided OSA into four major phenotypes. With this characterization in hand, the authors have reviewed the pharmacological treatments present to date according to the different phenotypes in which they could be used. Afterwards, they analyzed the efficacy of different medicaments for the therapy of the residual (despite CPAP treatment) excessive day-time sleepiness (EDS) that often afflicts OSA' patients. Expert opinion: Different drug classes have been evaluated, with some positive results. However, there is still the need to better define treatment strategies for every single phenotype. This underlines the importance to avoid considering the pathology like a single entity without any differences between each single form. The authors are concerned about the risk that, treating only EDS, patients could reduce their compliance to CPAP, thus not reducing the cardiovascular risk associated with OSA.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/terapia , Antidepressivos/uso terapêutico , Depressores do Apetite/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Humanos , Mandíbula/anatomia & histologia , Fenótipo , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/patologia
12.
Med Hypotheses ; 131: 109308, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443779

RESUMO

Adiposity is a chronic disease and one of the major modifiable risk factors for the development of type 2 diabetes mellitus (T2DM). Its prevalence in the world could be considered epidemic with 80% of patients with T2DM being obese. Novel antidiabetic drugs, such as glucagone-like peptide-1 (GLP-1) agonists have demonstrated benefitial effect on weight reduction. Nevertheless, in the last decades the need for new therapeutic strategies in the management of adiposity have emerged. Both adiposity and T2DM have negative effect on hypothalamic-pituitary-gonadal axis. Conversely, it has been known that sex hormone replacement therapy improves metabolic parameters in hypogonadal subjects. Recent research has found potential therapeutic effect of combination therapies with sex hormones and GLP-1 agonists in reducing body weight. Based on the aforementioned, we hypothesize that there is a possible synergistic effect of GLP-1 agonists and sex hormones on body mass reduction in patients with type 2 diabetes. The possible additional effect of sex hormones on weight loss could contribute to more effective treatment of T2DM and its complications.


Assuntos
Adiposidade/fisiologia , Fármacos Antiobesidade/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hormônios Esteroides Gonadais/farmacologia , Hipoglicemiantes/farmacologia , Modelos Biológicos , Perda de Peso , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/farmacologia , Depressores do Apetite/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Sinergismo Farmacológico , Estradiol/sangue , Feminino , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Masculino , Ciclo Menstrual/fisiologia , Sobrepeso/sangue , Sobrepeso/tratamento farmacológico , Sobrepeso/epidemiologia , Pâncreas/efeitos dos fármacos , Pâncreas/embriologia , Fatores de Risco , Taxa Secretória/efeitos dos fármacos , Testosterona/sangue , Perda de Peso/efeitos dos fármacos
13.
Genes (Basel) ; 10(8)2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398921

RESUMO

A dose of proanthocyanidins with satiating properties proved to be able to limit body weight increase several weeks after administration under exposure to a cafeteria diet. Here we describe some of the molecular targets and the duration of the effects. We treated rats with 500 mg grape seed proanthocyanidin extract (GSPE)/kg BW for ten days. Seven or seventeen weeks after the last GSPE dose, while animals were on a cafeteria diet, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to measure the mRNA of the key energy metabolism enzymes from the liver, adipose depots and muscle. We found that a reduction in the expression of adipose Lpl might explain the lower amount of adipose tissue in rats seven weeks after the last GSPE dose. The liver showed increased expression of Cpt1a and Hmgs2 together with a reduction in Fasn and Dgat2. In addition, muscle showed a higher fatty oxidation (Oxct1 and Cpt1b mRNA). However, after seventeen weeks, there was a completely different gene expression pattern. At the conclusion of the study, seven weeks after the last GSPE administration there was a limitation in adipose accrual that might be mediated by an inhibition of the gene expression of the adipose tissue Lpl. Concomitantly there was an increase in fatty acid oxidation in liver and muscle.


Assuntos
Adiposidade/efeitos dos fármacos , Depressores do Apetite/farmacologia , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Ocidental/efeitos adversos , Sobrepeso/prevenção & controle , Proantocianidinas/farmacologia , Tecido Adiposo/metabolismo , Animais , Depressores do Apetite/uso terapêutico , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Coenzima A-Transferases/genética , Coenzima A-Transferases/metabolismo , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Feminino , Leptina/genética , Leptina/metabolismo , Fígado/metabolismo , Músculo Esquelético/metabolismo , Sobrepeso/tratamento farmacológico , Proantocianidinas/uso terapêutico , Ratos , Vitis/química
14.
PLoS One ; 14(7): e0206271, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31318884

RESUMO

Broiler breeders, the parent stock of meat chickens, are feed-restricted throughout the production cycle to avoid obesity-related problems in their health and reproductive performance. Broiler breeders often show signs of chronic hunger, lack of satiety and feeding frustration, and the development of alternative feeding strategies has investigated the inclusion of calcium propionate (CaP) as an appetite suppressant. The mechanisms involved in the reduction of voluntary feed intake are unknown, but are thought to be due to low palatability, gastrointestinal discomfort, or both. The objective of this experiment was to examine the effect of CaP as an appetite suppressant on the experience of a negative affective state, using a conditioned place preference test. Twenty four broiler breeders were trained to associate the consumption of CaP or a placebo pill with a red or blue place, depending on inherent colour preference. Pullets consumed two pills followed by 20 g feed allotment. The CaP pill contained 160 mg of CaP and the placebo pill had 160 mg of feed. Conditioning lasted for 90 min/pullet/day over 8 consecutive days at 7 and 9 weeks of age, and pullets' choice was tested in a T-maze twice on two consecutive days at both 8 and 10 weeks of age. Data were analysed using a linear mixed regression model, with pen nested in the model and age as a repeated measure. Pullets were less likely to choose the place conditioned with the consumption of CaP (P<0.05) and the preference of the placebo linearly increased with training sessions (P<0.05). These results suggest that calcium propionate as an appetite suppressant can induce a negative affective state, reducing feed intake in broiler breeders fed CaP diets by causing an avoidance response rather than satiety.


Assuntos
Ração Animal , Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Propionatos/farmacologia , Animais , Galinhas , Feminino , Masculino
17.
AAPS J ; 21(4): 70, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31152318

RESUMO

Phenmetrazine, a selective dopamine and norepinephrine releaser, previously available as an oral anorectic, is prone to be abused. This study aimed to assess the feasibility of delivering phenmetrazine via the transdermal route for a new indication, while also minimizing its abuse potential. The passive permeation of phenmetrazine through dermatomed human cadaver skin was evaluated using static Franz diffusion cells at 10 mg/mL for the fumarate salt, and at 20, 40, and 80 mg/mL for the free base in propylene glycol for 24 h. Further, oleic acid (5% w/w), oleyl alcohol (5% and 10% w/w), and lauric acid (10% w/w) were investigated as chemical permeation enhancers to enhance the delivery. Skin irritation potential was assessed using EpiDerm™ in vitro reconstructed human epidermal model. The free base showed superior 24-h delivery (8.13 ± 4.07%, 10.6 ± 2.5%, and 10.4 ± 1.4% for groups with 20, 40, and 80 mg/mL of the free base, respectively) to phenmetrazine fumarate salt (undetectable). The successful screening of effective chemical enhancers, oleyl alcohol (5% and 10% w/w), oleic acid (5% w/w), and lauric acid (10% w/w) resulted in significant enhancement of delivery. The calculated therapeutic relevant flux for the potential indication, attention deficit hyperactivity disorder, 20 µg/cm2/h was met, where a 24-mg daily dose from a 50-cm2 patch was projected to be delivered to a 60-kg individual. Irritation study results suggest that formulations with therapeutically relevant delivery are likely to be non-irritant. In conclusion, it is feasible to deliver therapeutically relevant amounts of phenmetrazine via the transdermal route.


Assuntos
Depressores do Apetite/farmacocinética , Dermatite Irritante/etiologia , Fenmetrazina/farmacocinética , Pele/metabolismo , Administração Cutânea , Depressores do Apetite/administração & dosagem , Depressores do Apetite/toxicidade , Dermatite Irritante/metabolismo , Composição de Medicamentos , Reposicionamento de Medicamentos , Estudos de Viabilidade , Humanos , Técnicas In Vitro , Fenmetrazina/administração & dosagem , Fenmetrazina/toxicidade , Pele/efeitos dos fármacos , Absorção Cutânea , Testes de Irritação da Pele
18.
Metabolism ; 96: 83-91, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30902750

RESUMO

BACKGROUND: This pilot study evaluated whether adding phentermine to liraglutide would induce further weight loss in participants who had previously lost weight with liraglutide alone. SUBJECTS/METHODS: Participants were 45 adults with obesity (75.6% female, 55.6% white, body mass index = 34.3 ±â€¯4.7 kg/m2) who had lost an average of 12.6 ±â€¯6.8% of initial weight during a prior 1-year randomized trial with liraglutide and intensive behavioral treatment. Participants were re-randomized, in a double-blinded fashion, to liraglutide 3.0 mg plus phentermine 15.0 mg (liraglutide-phentermine) or liraglutide plus placebo (liraglutide-placebo). Participants also were provided with four, 15-minute counseling sessions during the 12-week extension study. RESULTS: At week 12, the liraglutide-phentermine and liraglutide-placebo groups lost a mean (±SEM) of 1.6 ±â€¯0.6% and 0.1 ±â€¯0.5% of re-randomization weight, respectively (p = 0.073). Two (9.1%) liraglutide-phentermine participants and one (4.3%) liraglutide-placebo participant lost ≥5% of re-randomization weight; 19 (86.4%) and 16 (69.9%) participants, respectively, maintained their full weight loss achieved in the prior 1-year trial (p = 0.125). Liraglutide-phentermine participants generally reported larger reductions in hunger and food preoccupation than liraglutide-placebo participants during the first 8 weeks of the extension study. CONCLUSIONS: The combination of liraglutide and phentermine appeared to be well-tolerated but did not produce additional clinically meaningful weight loss in individuals who had already lost 12.6% of initial weight with liraglutide alone. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02911818.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Adulto , Idoso , Fármacos Antiobesidade/efeitos adversos , Apetite/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Fome/efeitos dos fármacos , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Fentermina/efeitos adversos , Projetos Piloto , Resultado do Tratamento , Perda de Peso
20.
J Nutr ; 149(3): 362-365, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30722047

RESUMO

Oleoylethanolamide is a well-recognized anorectic compound which also has noteworthy effects on food-reward, influencing the acetylcholine (ACh)/dopamine (DA) balance in the cholinergic system. After its administration, oleoylethanolamide is quickly degraded into oleic acid and ethanolamine. The effect of oleic acid on the gut-brain axis has been extensively investigated, whereas ethanolamine has received scarce attention. However, there is scattered evidence from old and recent research that has underlined the influence of ethanolamine on the cholinergic system. In the present article, we propose a model by which the released ethanolamine contributes to the overall balance between DA and ACh after oleoylethanolamide administration.


Assuntos
Acetilcolina/metabolismo , Dopamina/metabolismo , Endocanabinoides/farmacologia , Etanolamina/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Animais , Depressores do Apetite/metabolismo , Depressores do Apetite/farmacologia , Endocanabinoides/metabolismo , Humanos , Camundongos , Modelos Biológicos , Ácidos Oleicos/metabolismo , Ratos
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