RESUMO
Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon.
Assuntos
Proteínas de Peixes/metabolismo , Peixes/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Sequência de Aminoácidos , Animais , Depressores do Apetite/administração & dosagem , Depressores do Apetite/metabolismo , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/genética , Regulação do Apetite/fisiologia , Sequência de Bases , Clonagem Molecular , Duodeno/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Proteínas de Peixes/administração & dosagem , Proteínas de Peixes/genética , Peixes/genética , Peixes/fisiologia , Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraperitoneais , Polipeptídeo Amiloide das Ilhotas Pancreáticas/administração & dosagem , Polipeptídeo Amiloide das Ilhotas Pancreáticas/genética , Filogenia , Homologia de Sequência de Aminoácidos , Distribuição TecidualRESUMO
The hypothalamic peptide oxytocin and its receptor are involved in a range of physiological processes, including parturition, lactation, cell growth, wound healing, and social behavior. More recently, increasing evidence has established the effects of oxytocin on food intake, energy expenditure, and peripheral metabolism. In this review, we provide a comprehensive description of the central oxytocinergic system in which oxytocin acts to shape eating behavior and metabolism. Next, we discuss the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization. A brief summary of oxytocin actions learned from animal models is presented, showing that weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis. Following an in-depth discussion on the technical challenges related to endogenous oxytocin measurements in humans, we synthesize data related to the association between endogenous oxytocin levels, weight status, metabolic syndrome, and bone health. We then review clinical trials showing that in humans, acute oxytocin administration reduces food intake, attenuates fMRI activation of food motivation brain areas, and increases activation of self-control brain regions. Further strengthening the role of oxytocin in appetite regulation, we review conditions of hypothalamic insult and certain genetic pathologies associated with oxytocin depletion that present with hyperphagia, extreme weight gain, and poor metabolic profile. Intranasal oxytocin is currently being evaluated in human clinical trials to learn whether oxytocin-based therapeutics can be used to treat obesity and its associated sequela. At the end of this review, we address the fundamental challenges that remain in translating this line of research to clinical care.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Apetite/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ocitocina/farmacologia , Ocitocina/uso terapêutico , Animais , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Motivação/efeitos dos fármacos , Obesidade/metabolismoRESUMO
This paper reviews provenance, chemical composition and properties of tea (Camelia sinensis L.) and coffee (Coffee arabica, L. and Coffeacaniphora, L.), their general health effects, as well as the currently available knowledge concerning their action on fat storage, physiological mechanisms of their effects, as well as their safety and recommended dosage for treatment of obesity. Both tea and coffee possess the ability to promote health and to prevent, to mitigate and to treat numerous disorders. This ability can be partially due to presence of caffeine in both plants. Further physiological and medicinal effects could be explained by other molecules (theaflavins, catechins, their metabolites and polyphenols in tea and polyphenol chlorogenic acid in coffee). These plants and plant molecules can be efficient for prevention and treatment of numerous metabolic disorders including metabolic syndrome, cardiovascular diseases, type 2 diabetes and obesity. Both plants and their constituents can reduce fat storage through suppression of adipocyte functions, and support of gut microbiota. In addition, tea can prevent obesity via reduction of appetite, food consumption and food absorption in gastrointestinal system and through the changes in fat metabolism.
Assuntos
Fármacos Antiobesidade/administração & dosagem , Café , Nível de Saúde , Obesidade/prevenção & controle , Compostos Fitoquímicos/administração & dosagem , Chá , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/efeitos adversos , Regulação do Apetite/efeitos dos fármacos , Café/efeitos adversos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/diagnóstico , Obesidade/fisiopatologia , Compostos Fitoquímicos/efeitos adversos , Chá/efeitos adversos , Aumento de Peso/efeitos dos fármacosRESUMO
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 JovemRESUMO
Human obesity is accompanied by alterations in the blood concentrations of multiple circulating appetite regulators. Paradoxically, most of the appetite-inhibitory hormones are elevated in nonsyndromic obesity, while most of the appetite stimulatory hormones are reduced, perhaps reflecting vain attempts of regulation by inefficient feedback circuitries. In this context, it is important to understand which appetite regulators exhibit a convergent rather than paradoxical behavior and hence are likely to contribute to the maintenance of the obese state. Pharmacological interventions in obesity should preferentially consist of the supplementation of deficient appetite inhibitors or the neutralization of excessive appetite stimulators. Here, we critically analyze the current literature on appetite-regulatory peptide hormones. We propose a short-list of appetite modulators that may constitute the best candidates for therapeutic interventions.
Assuntos
Regulação do Apetite , Obesidade , Regulação do Apetite/efeitos dos fármacos , Suplementos Nutricionais , Hormônios , Humanos , Obesidade/terapiaRESUMO
Obesity is associated with altered glycine metabolism in humans. This study investigated the mechanisms regulating glycine metabolism in obese rats. Eight-week-old Zucker diabetic fatty rats (ZDF; a type-II diabetic animal model) received either 1% glycine or 1.19% L-alanine (isonitrogenous control) in drinking water for 6 weeks. An additional group of lean Zucker rats also received 1.19% L-alanine as a lean control. Glycine concentrations in serum and liver were markedly lower in obese versus lean rats. Enteral glycine supplementation restored both serum and hepatic glycine levels, while reducing mesenteric and internal white fat mass compared with alanine-treated ZDF rats. Blood glucose and non-esterified fatty acid (NEFA) concentrations did not differ between the control and glycine-supplemented ZDF rats (P > 0.10). Both mRNA and protein expression of aminomethyltransferase (AMT) and glycine dehydrogenase, decarboxylating (GLDC) were increased in the livers of obese versus lean rats (P < 0.05). In contrast, glycine cleavage system H (GCSH) hepatic mRNA expression was downregulated in obese versus lean rats, although there was no change in protein expression. These findings indicate that reduced quantities of glycine observed in obese subjects likely results from an upregulation of the hepatic glycine cleavage system and that dietary glycine supplementation potentially reduces obesity in ZDF rats.
Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Glicina/administração & dosagem , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Tecido Adiposo Branco/metabolismo , Alanina/administração & dosagem , Alanina/metabolismo , Aminometiltransferase/genética , Aminometiltransferase/metabolismo , Animais , Regulação do Apetite/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Glicina/metabolismo , Proteína H do Complexo Glicina Descarboxilase/genética , Proteína H do Complexo Glicina Descarboxilase/metabolismo , Glicina Desidrogenase (Descarboxilante)/genética , Glicina Desidrogenase (Descarboxilante)/metabolismo , Fígado/metabolismo , Masculino , Obesidade/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos ZuckerRESUMO
The endocannabinoid system (ECs) is a well known contributor to the hedonic regulation of food intake (FI) in mammals whereas in fish, the knowledge regarding hedonic mechanisms that control FI is limited. Previous studies reported the involvement of ECs in FI regulation in fish since anandamide (AEA) treatment induced enhanced FI and changes of mRNA abundance of appetite-related neuropeptides through cannabinoid receptor 1 (cnr1). However, no previous studies in fish evaluated the impact of palatable food like high-fat diets (HFD) on mechanisms involved in hedonic regulation of FI including the possible involvement of ECs. Therefore, we aimed to evaluate the effect of feeding a HFD on the response of ECs in rainbow trout (Oncorhynchus mykiss). First, we demonstrated a higher intake over 4â¯days of HFD compared with a control diet (CD). Then, we evaluated the postprandial response (1, 3 and 6â¯h) of components of the ECs in plasma, hypothalamus, and telencephalon after feeding fish with CD and HFD. The results obtained indicate that the increased FI of HFD occurred along with increased levels of 2-arachidonoylglycerol (2-AG) and AEA in plasma and in brain areas like hypothalamus and telencephalon putatively involved in hedonic regulation of FI in fish. Decreased mRNA abundance of EC receptors like cnr1, gpr55 and trpv1 suggest a feed-back counter-regulatory mechanism in response to the increased levels of EC. Furthermore, the results also suggest that neural activity players associated to FI regulation in mammals as cFOS, γ-Amino butyric acid (GABA) and brain derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase (NTRK) systems could be involved in the hedonic eating response to a palatable diet in fish.
Assuntos
Dieta Hiperlipídica , Endocanabinoides/metabolismo , Oncorhynchus mykiss/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Animais , Apetite/efeitos dos fármacos , Apetite/genética , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Gorduras na Dieta/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/genética , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Neuropeptídeos/efeitos dos fármacos , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Oncorhynchus mykiss/fisiologia , Receptor CB1 de Canabinoide/genética , Telencéfalo/efeitos dos fármacos , Telencéfalo/metabolismoRESUMO
The pig is a valuable animal model to study obesity in humans due to the physiological similarity between humans and pigs in terms of digestive and associated metabolic processes. The dietary use of vegetal protein, probiotics and omega-3 fatty acids is recommended to control weight gain and to fight obesity-associated metabolic disorders. Likewise, there are recent reports on their beneficial effects on brain functions. The hypothalamus is the central part of the brain that regulates food intake by means of the production of food intake-regulatory hypothalamic neuropeptides, as neuropeptide Y (NPY), orexin A and pro-opiomelanocortin (POMC), and neurotransmitters, such as dopamine and serotonin. Other mesolimbic areas, such as the hippocampus, are also involved in the control of food intake. In this study, the effect of a high fat diet (HFD) alone or supplemented with these additives on brain neuropeptides and neurotransmitters was assessed in forty-three young pigs fed for 10 weeks with a control diet (T1), a high fat diet (HFD, T2), and HFD with vegetal protein supplemented with Bifidobacterium breve CECT8242 alone (T3) or in combination with omega-3 fatty acids (T4). A HFD provoked changes in regulatory neuropeptides and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and alterations mostly in the dopaminergic system in the ventral hippocampus. Supplementation of the HFD with B. breve CECT8242, especially in combination with omega-3 fatty acids, was able to partially reverse the effects of HFD. Correlations between productive and neurochemical parameters supported these findings. These results confirm that pigs are an appropriate animal model alternative to rodents for the study of the effects of HFD on weight gain and obesity. Furthermore, they indicate the potential benefits of probiotics and omega-3 fatty acids on brain function.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Probióticos/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/análise , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Neuropeptídeos/análise , Neurotransmissores/análise , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/prevenção & controle , Suínos , Aumento de Peso/efeitos dos fármacosRESUMO
Atypical antipsychotics (AAPs) have the tendency of inducing severe metabolic alterations like obesity, diabetes mellitus, insulin resistance, dyslipidemia and cardiovascular complications. These alterations have been attributed to altered hypothalamic appetite regulation, energy sensing, insulin/leptin signaling, inflammatory reactions and active reward anticipation. Line of evidence suggests that transient receptor potential vanilloid type 1 and 3 (TRPV1 and TRPV3) channels are emerging targets in treatment of obesity, diabetes mellitus and could modulate feed intake. The present study was aimed to investigate the putative role TRPV1/TRPV3 in olanzapine-induced metabolic alterations in mice. Female BALB/c mice were treated with olanzapine for six weeks to induce metabolic alterations. Non-selective TRPV1/TRPV3 antagonist (ruthenium red) and selective TRPV1 (capsazepine) and TRPV3 antagonists (2,2-diphenyltetrahydrofuran or DPTHF) were used to investigate the involvement of TRPV1/TRPV3 in chronic olanzapine-induced metabolic alterations. These metabolic alterations were differentially reversed by ruthenium red and capsazepine, while DPTHF didn't show any significant effect. Olanzapine treatment also altered the mRNA expression of hypothalamic appetite-regulating and nutrient-sensing factors, inflammatory genes and TRPV1/TRPV3, which were reversed with ruthenium red and capsazepine treatment. Furthermore, olanzapine treatment also increased expression of TRPV1/TRPV3 in nucleus accumbens (NAc), TRPV3 expression in ventral tegmental area (VTA), which were reversed by the respective antagonists. However, DPTHF treatment showed reduced feed intake in olanzapine treated mice, which might be due to TRPV3 specific antagonism and reduced hedonic feed intake. In conclusion, our results suggested the putative role TRPV1 in hypothalamic dysregulations and TRPV3 in the mesolimbic pathway; both regulate feeding in olanzapine treated mice.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Inflamação/metabolismo , Olanzapina/farmacologia , Canais de Cátion TRPV/metabolismo , Animais , Capsaicina/administração & dosagem , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Corantes/administração & dosagem , Corantes/farmacologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Furanos/administração & dosagem , Furanos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Teste de Tolerância a Glucose , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Hipotálamo/efeitos dos fármacos , Inflamação/genética , Metformina/administração & dosagem , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Atividade Motora , Rutênio Vermelho/administração & dosagem , Rutênio Vermelho/farmacologia , Fármacos do Sistema Sensorial/administração & dosagem , Fármacos do Sistema Sensorial/farmacologia , Canais de Cátion TRPV/genéticaRESUMO
Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a popular nutraceutical used for weight management and appetite control. We sought to determine the physiological benefits of RK on the meal patterns and cardiovascular changes associated with an obesogenic diet. In addition, we explored whether the physiological benefits of RK promoted anxiety-related behaviors. Male and female C57BL/6J mice were administered a daily oral gavage of RK 200 mg/kg, RK 400 mg/kg, or vehicle for 14 days. Commencing with dosing, mice were placed on a high-fat diet (45% fat) or low-fat diet (10% fat). Our results indicated that RK 200 mg/kg had a differential influence on meal patterns in males and females. In contrast, RK 400 mg/kg reduced body weight gain, open-field total distance travelled, hemodynamic measures (i.e., reduced systolic blood pressure (BP), diastolic BP and mean BP), and increased nocturnal satiety ratios in males and females. In addition, RK 400 mg/kg increased neural activation in the nucleus of the solitary tract, compared with vehicle. RK actions were not influenced by diet, nor resulted in an anxiety-like phenotype. Our findings suggest that RK has dose-differential feeding and cardiovascular actions, which needs consideration as it is used as a nutraceutical for weight control for obesity.
Assuntos
Butanonas/administração & dosagem , Butanonas/farmacologia , Suplementos Nutricionais , Comportamento Alimentar/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Obesidade/prevenção & controle , Animais , Regulação do Apetite/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Resposta de Saciedade/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
Momardica charint seed as vegetable and folk medicine in Pakistan, India, China, Bangladesh and other Asian countries Momardica charinta also known as Kerala, bittergourd ,balsam pear. It possesses many biological active constituents including glycosides, saponins, phenolic and flavonoids compound, protein, triterpenes, steroid, saponins, alkaloid. It also contain thiamine ,beta carotene, folate, riboflavin, calcium, iron, potassium, zinc and fiber. Several studies have been done to show medicinal importance of its fruit which has different biological functions such as anti-diabetes antihypertension, antiviral, antibacterial and antifungal infection, anti-tumorous as well as anti-carcinogenic effects. The present research is big contribution of Momardicacharinta activity as weight reducing plant through serotonergic neurotransmitter Decrease in body weight and food intake might be due to increased concentration of serotonin in their respective receptors in brain, which produce hypophagic effect in rats treated with water extract of Momardicacharinttia. More animal and human trials needed to confirm, the safety and antiobesity effect of MC and the role of neurotransmitter involve in reduction of body weight.
Assuntos
Depressores do Apetite/farmacologia , Regulação do Apetite/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Momordica charantia , Extratos Vegetais/farmacologia , Serotonina/metabolismo , Redução de Peso/efeitos dos fármacos , Animais , Depressores do Apetite/isolamento & purificação , Encéfalo/metabolismo , Frutas , Masculino , Momordica charantia/química , Extratos Vegetais/isolamento & purificação , RatosRESUMO
Amphetamine (AMPH), an appetite suppressant, alters expression levels of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus. This study explored the potential role of cJun-N-terminal kinases (JNK) in appetite control, mediated by reactive oxygen species (ROS) and activator protein-1 (AP-1) in AMPH-treated rats. Rats were given AMPH daily for 4 days. Changes in feeding behavior and expression levels of hypothalamic NPY, CART, cFos, cJun, phosphorylated JNK (pJNK), as well as those of anti-oxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione S-transferase (GST), were examined and compared. Following AMPH treatment, food intake and NPY expression decreased, whereas the other proteins expression and AP-1/DNA binding activity increased. Both cerebral cJun inhibition and ROS inhibition attenuated AMPH anorexia and modified detected protein, revealing a crucial role for AP-1 and ROS in regulating AMPH-induced appetite control. Moreover, both pJNK/CART and SOD/CART activities detected by double immunofluorescent staining increased in hypothalamic arcuate nucleus in AMPH-treated rats. The results suggested that pJNK/AP-1 signaling and endogenous anti-oxidants participated in regulating NPY/CART-mediated appetite control in rats treated with AMPH. These findings advance understanding of the molecular mechanism underlying the role of pJNK/AP-1 and oxidative stress in NPY/CART-mediated appetite suppression in AMPH-treated rats.
Assuntos
Regulação do Apetite/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Neuropeptídeo Y/fisiologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição AP-1/fisiologia , Anfetamina/farmacologia , Animais , Antracenos/administração & dosagem , Antracenos/farmacologia , Antioxidantes/metabolismo , Regulação do Apetite/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Imunofluorescência , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Infusões Intraventriculares , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeo Y/biossíntese , Ratos , Transdução de Sinais/fisiologia , Fator de Transcrição AP-1/metabolismoRESUMO
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 , Redução 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 TratamentoRESUMO
Consumption of non-starch polysaccharides (NSP) is associated with reduced risk of obesity. This study aimed to compare the effects of cereals (oats) and legumes (soybean), rich in different classes of NSP, on appetite regulation and fat accumulation in rats. Soy pectin fermented more efficient than cereal arabinoxylan in rats. Soy pectin and oat ß-glucan were utilized mainly in the caecum of rats. Only small amount of maltodextrin, cello-oligosaccharides and xylo-oligosaccharides were detected in the digesta. Caecal fermentation of soy pectin produced significantly higher concentration of short chain fatty acids (SCFAs) compared to the control. Retroperitoneal (RP) fat-pad weight was significantly lower for rats fed with soybean meal enriched diet than for controls. An inverse correlation between rat RP fat-pad weight and concentration (and proportion) of butyrate was observed. Consumption of soy pectin and oat ß-glucan enriched foods to produce targeted SCFAs in vivo could be a potential strategy to lower fat mass accumulation and a potential tool to manage obesity.
Assuntos
Avena/química , Glycine max/química , Obesidade/prevenção & controle , Polissacarídeos/química , Animais , Regulação do Apetite/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/metabolismo , Fibras na Dieta/farmacologia , Digestão/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Humanos , Obesidade/metabolismo , Pectinas/farmacologia , Polissacarídeos/farmacologia , Ratos , beta-Glucanas/farmacologiaRESUMO
BACKGROUND AND OBJECTIVES: Delivery of nutrients directly to the small intestine, either via enteral feeding tube or by gastric bypass surgery, is associated with increased levels of appetite-suppressing and glucoregulatory hormones, including GLP-1, and reduced appetite. Achieving these changes non-invasively using formulated foods may be of therapeutic benefit in individuals with obesity and related comorbidities. The aim of this pilot study was to determine the effect of a single dose of a novel delayed-release nutrient (DRN) on glucose, GLP-1, c-peptide, insulin, and appetite in adults with obesity and type 2 diabetes. SUBJECTS AND METHODS: We formulated an all-natural, generally recognized as safe ('GRAS") DRN and conducted a randomized prospective crossover trial. Nineteen adults with obesity and type 2 diabetes underwent paired 3-h meal tolerance tests (MTT) in randomized order 1-4 weeks apart. Subjects ingested a single dose of DRN and the same nutrients as unformulated powders (UN). RESULTS: For DRN compared with UN, the maximal concentration (Cmax) was significantly lower for glucose, c-peptide, and insulin, and the time of maximal concentration (Tmax) was significantly delayed. While Tmax for GLP-1 was also significantly delayed following DRN compared with UN (45 min later; p = 0.26), Cmax did not differ significantly. GLP-1 rose significantly during the last 90 min of the 3-h MTT (ß1 = 0.16 pg/mL/min, p = 0.025), while following UN it decreased (ß1 = -0.21 pg/mL/min, p = 0.0026) (p difference = 0.0003). There were minimal differences in seven measures of appetite and adverse symptoms between DRN and UN. CONCLUSIONS: We conclude that nutrient can be formulated using all-natural ingredients to induce a delayed rise in GLP-1. Further testing is needed to determine the amount and site of nutrient release, when maximum GLP-1 levels occur, and if modification of the formulation specifications and dose are associated with appetite and glucose control.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Apetite/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Peptídeo 1 Semelhante ao Glucagon/sangue , Obesidade/tratamento farmacológico , Adulto , Glicemia , Peptídeo C/sangue , Estudos Cross-Over , Ingestão de Energia/efeitos dos fármacos , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
This paper reports on the successful management of hyperphagia (exaggerated hunger) in a 14yr-old female with Prader-Willi syndrome (PWS). This child was diagnosed with PWS, (maternal uniparental disomy) at 18 months due to developmental delay, hypertonia, weight gain and extreme eating behaviour. Treatment of a supplement for appetite suppression commenced at 2 years of age. This single-case records ingestion of an Indian cactus succulent Caralluma fimbriata extract (CFE) over 12 years, resulting in anecdotal satiety, free access to food and management of weight within normal range. CFE was administered in a drink daily and dose was slowly escalated by observation for appetite suppression. Rigorous testing determined blood count, vitamins, key minerals, HbA1c, IGF-1 and function of the liver and thyroid all within normal range. The report suggests a strategy for early intervention against hyperphagia and obesity in PWS. This case was the instigator of the successful Australian PWS/CFE pilot and though anecdotal, the adolescent continues to ingest CFE followed by paediatricians at the Royal Children's Hospital Melbourne, Victoria, Australia. Future clinical trials are worth considering, to determine an appropriate dose for individuals with PWS.
Assuntos
Apocynaceae/química , Regulação do Apetite/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Síndrome de Prader-Willi/dietoterapia , Adolescente , Contagem de Células Sanguíneas , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Minerais/sangue , Extratos Vegetais/química , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/patologia , Glândula Tireoide/efeitos dos fármacos , Vitaminas/sangueRESUMO
The mammalian hypothalamus regulates key homeostatic and neuroendocrine functions ranging from circadian rhythm and energy balance to growth and reproductive cycles via the hypothalamic-pituitary and hypothalamic-thyroid axes. In addition to its neurones, tanycytes are taking centre stage in the short- and long-term augmentation and integration of diverse hypothalamic functions, although the genetic regulators and mediators of their involvement are poorly understood. Exogenous interventions have implicated fibroblast growth factor (FGF) signalling, although the focal point of the action of FGF and any role for putative endogenous players also remains elusive. We carried out a comprehensive high-resolution screen of FGF signalling pathway mediators and modifiers using a combination of in situ hybridisation, immunolabelling and transgenic reporter mice, aiming to map their spatial distribution in the adult hypothalamus. Our findings suggest that ß-tanycytes are the likely focal point of exogenous and endogenous action of FGF in the third ventricular wall, utilising FGF receptor (FGFR)1 and FGFR2 IIIc isoforms, but not FGFR3. Key IIIc-activating endogenous ligands include FGF1, 2, 9 and 18, which are expressed by a subset of ependymal and parenchymal cells. In the parenchymal compartment, FGFR1-3 show divergent patterns, with FGFR1 being predominant in neuronal nuclei and expression of FGFR3 being associated with glial cell function. Intracrine FGFs are also present, suggestive of multiple modes of FGF function. Our findings provide a testable framework for understanding the complex role of FGFs with respect to regulating the metabolic endocrine and neurogenic functions of hypothalamus in vivo.
Assuntos
Regulação do Apetite/genética , Metabolismo Energético/genética , Células Ependimogliais/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Hipotálamo/citologia , Animais , Regulação do Apetite/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Feminino , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Obesity as a multifactorial disorder has been shown a dramatically growing trend recently. Besides genetic and environmental factors, dysregulation of the endocannabinoid system tone is involved in the pathogenesis of obesity. This study reviewed the potential efficacy of Oleoylethanolamide (OEA) as an endocannabinoid-like compound in the energy homeostasis and appetite control in people with obesity. OEA as a lipid mediator and bioactive endogenous ethanolamide fatty acid is structurally similar to the endocannabinoid system compounds; nevertheless, it is unable to induce to the cannabinoid receptors. Unlike endocannabinoids, OEA negatively acts on the food intake and suppress appetite via various mechanisms. Indeed, OEA as a ligand of PPAR-α, GPR-119, and TRPV1 receptors participates in the regulation of energy intake and energy expenditure, feeding behavior, and weight gain control. OEA delays meal initiation, reduces meal size, and increases intervals between meals. Considering side effects of some approaches used for the management of obesity such as antiobesity drugs and surgery as well as based on sufficient evidence about the protective effects of OEA in the improvement of common abnormalities in people with obese, its supplementation as a novel efficient and FDA approved pharmaceutical agent can be recommended.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Endocanabinoides/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Obesidade/tratamento farmacológico , Ácidos Oleicos/uso terapêutico , Endocanabinoides/genética , Endocanabinoides/metabolismo , Ácidos Graxos/metabolismo , Humanos , Lipídeos/genética , Obesidade/genética , Obesidade/patologia , Ácidos Oleicos/genética , PPAR alfa/metabolismo , Receptores Acoplados a Proteínas G/genética , Canais de Cátion TRPV/genéticaRESUMO
BACKGROUND: Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio-melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). OBJECTIVES: We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. METHODS: Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. RESULTS: Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11ß-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1ß, IL-6, and TNFα) was reduced. CONCLUSIONS: Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative -defense, and inflammatory responses of this homeostasis- regulating center.
Assuntos
Antioxidantes/farmacologia , Metabolismo Energético/efeitos dos fármacos , Frutose/metabolismo , Hipotálamo/metabolismo , Ração Animal , Animais , Antioxidantes/metabolismo , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/fisiologia , Dieta , Metabolismo Energético/fisiologia , Feminino , Insulina/metabolismo , Leptina/metabolismo , Neuropeptídeo Y/metabolismo , Neuropeptídeos/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ratos Wistar , Receptores para Leptina/efeitos dos fármacos , Receptores para Leptina/metabolismo , Estresse FisiológicoRESUMO
Multiple stimulatory and inhibitory neural circuits control eating, and these circuits are influenced by an array of hormonal, neuropeptide, and neurotransmitter signals. For example, estrogen and oxytocin (OT) both are known to decrease food intake, but the mechanisms by which these signal molecules influence eating are not fully understood. These studies investigated the interaction between estrogen and OT in the control of food intake. RT-qPCR studies revealed that 17ß-estradiol benzoate (EB)-treated rats showed a two-fold increase in OT mRNA in the paraventricular nucleus of the hypothalamus (PVN) compared to Oil-treated controls. Increased OT mRNA expression may increase OT protein levels, and immunohistochemistry studies showed that EB-treated rats had more intense OT labeling in the nucleus of the solitary tract (NTS), a region known to integrate signals for food intake. Food intake measurements showed that EB treatment reduced food intake, as expected. EB-treated rats lost weight over the course of the experiment, as expected, and EB-treated rats that received the highest dose of OT lost more weight than EB-treated rats that did not receive OT. Finally, OT antagonist administered to EB-treated rats reversed the effect of EB on food intake, suggesting that estrogen effects to decrease food intake may involve the oxytocinergic pathway.