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1.
J Agric Food Chem ; 68(10): 3149-3162, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32062961

RESUMO

Moringa oleifera Lam. (MO), which is widely consumed as both food and herbal medicine in tropical and subtropical regions, has a wide spectrum of health benefits. Yet, whether the oil obtained from MO seeds could affect (improve) the sleep activity remains unclear. Herein, we used the locomotor activity, pentobarbital-induced sleeping, and pentetrazol-induced convulsions test to examine sedative-hypnotic effects (SHE) of MO oil (MOO) and explored the underlying mechanisms. Besides, the main components of MOO like oleic acid, ß-Sitosterol, and Stigmasterol were also evaluated. The results showed that they possessed good SHE. Except for oleic acid and Stigmasterol, they could significantly elevate γ-amino butyric acid (GABA) and reduce glutamic acid (Glu) levels in the hypothalamus of mice. Moreover, SHE was blocked by picrotoxin, flumazenil, and bicuculline, except for oleic acid, which could not be antagonized by picrotoxin. Molecular mechanisms showed that MOO and ß-Sitosterol significantly upregulated the amount of protein-level expression of Glu decarboxylase-65 (GAD65) and α1-subunit of GABAA receptors in the hypothalamus of mice, not affecting GAD67, γ2 subunits. These data indicated that MOO modulates sleep architectures via activation of the GABAA-ergic systems.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Moringa oleifera/química , Pentobarbital/administração & dosagem , Extratos Vegetais/administração & dosagem , Óleos Vegetais/administração & dosagem , Receptores de GABA-A/metabolismo , Sono/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Receptores de GABA-A/genética , Sementes/química , Ácido gama-Aminobutírico/genética
2.
Nat Commun ; 11(1): 640, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005806

RESUMO

Reduced food intake is common to many pathological conditions, such as infection and toxin exposure. However, cortical circuits that mediate feeding responses to these threats are less investigated. The anterior insular cortex (aIC) is a core region that integrates interoceptive states and emotional awareness and consequently guides behavioral responses. Here, we demonstrate that the right-side aIC CamKII+ (aICCamKII) neurons in mice are activated by aversive visceral signals. Hyperactivation of the right-side aICCamKII neurons attenuates food consumption, while inhibition of these neurons increases feeding and reverses aversive stimuli-induced anorexia and weight loss. Similar manipulation at the left-side aIC does not cause significant behavioral changes. Furthermore, virus tracing reveals that aICCamKII neurons project directly to the vGluT2+ neurons in the lateral hypothalamus (LH), and the right-side aICCamKII-to-LH pathway mediates feeding suppression. Our studies uncover a circuit from the cortex to the hypothalamus that senses aversive visceral signals and controls feeding behavior.


Assuntos
Agentes Aversivos/toxicidade , Córtex Cerebral/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Córtex Cerebral/efeitos dos fármacos , Feminino , Região Hipotalâmica Lateral/metabolismo , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
3.
Gen Comp Endocrinol ; 285: 113264, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469997

RESUMO

Thyroid hormone (TH) is involved in regulating the reproduction of vertebrates. Its physiological action in the target tissues is due to the conversion of TH by iodothyronine deiodinases. In this study, we aimed to clone and characterize type 2 (sdDio2) and type 3 (sdDio3) of the sapphire devil Chrysiptera cyanea, a tropical damselfish that undergoes active reproduction under long-day conditions, and to study the involvement of THs in the ovarian development of this species. When the cDNAs of sdDio2 and sdDio3 were partially cloned, they had deduced amino acid sequences of lengths 271 and 267, respectively, both of which were characterized by one selenocysteine residue. Real-time quantitative PCR (qPCR) revealed that both genes are highly expressed in the whole brain, and sdDio2 and sdDio3 are highly transcribed in the liver and ovary, respectively. In situ hybridization analyses showed positive signals of sdDio2 and sdDio3 transcripts in the hypothalamic area of the brain. Little change in mRNA abundance of sdDio2 and sdDio3 in the brain was observed during the vitellogenic phases. It is assumed that simultaneous activation and inactivation of THs occur in this area because oral administration of triiodothyronine (T3), but not of thyroxine (T4), upregulated mRNA abundance of both genes in the brain. The transcript levels of sdDio2 in the liver and sdDio3 in the ovary increased as vitellogenesis progressed, suggesting that, through the metabolism of THs, sdDio2 and sdDio3 play a role in vitellogenin synthesis in the liver and yolk accumulation/E2 synthesis in the ovary. Taken together, these results suggest that iodothyronine deiodinases act as a driver for vitellogenesis in tropical damselfish by conversion of THs in certain peripheral tissues.


Assuntos
Perfilação da Expressão Gênica , Iodeto Peroxidase/genética , Perciformes/genética , Clima Tropical , Vitelogênese/genética , Animais , Feminino , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Iodeto Peroxidase/metabolismo , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Perciformes/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Hormônios Tireóideos/administração & dosagem , Hormônios Tireóideos/farmacologia , Distribuição Tecidual , Vitelogênese/efeitos dos fármacos
4.
Ecotoxicol Environ Saf ; 188: 109912, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706240

RESUMO

Synthetic progestins are emerging contaminants of the aquatic environment with endocrine disrupting potential. The main aim of the present study was to investigate the effects of the synthetic progestins gestodene, and drospirenone on sex differentiation in common carp (Cyprinus carpio) by histological analysis. To gain insights into the mechanisms behind the observations from the in vivo experiment on sex differentiation, we analyzed expression of genes involved in hypothalamus-pituitary-gonad (HPG) and hypothalamus-pituitary-thyroid (HPT) axes, histology of hepatopancreas, and in vitro bioassays. Carp were continuously exposed to concentrations of 2 ng/L of single progestins (gestodene or drospirenone) or to their mixture at concentration 2 ng/L of each. The exposure started 24 h after fertilization of eggs and concluded 160 days post-hatching. Our results showed that exposure of common carp to a binary mixture of drospirenone and gestodene caused increased incidence of intersex (32%) when compared to clean water and solvent control groups (both 3%). Intersex most probably was induced by a combination of multiple modes of action of the studied substances, namely anti-gonadotropic activity, interference with androgen receptor, and potentially also with HPT axis or estrogen receptor.


Assuntos
Androstenos/toxicidade , Carpas/crescimento & desenvolvimento , Disruptores Endócrinos/toxicidade , Norpregnenos/toxicidade , Diferenciação Sexual/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Hepatopâncreas/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Diferenciação Sexual/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-31887407

RESUMO

In order to evaluate fatty acid (FA) sensing systems based on binding to FAT/CD36 in hypothalamus of Chinese perch (Siniperca chuatsi) and its sensitivity to FAs with the same chain length and different unsaturation levels. The effects of Stearate (SA; C18:0), oleate (OA; C18:1 n-9), linoleic acid (LA; C18:2 n-6), and α-linolenic acid (ALA; C18:3 n-3) on hypothalamic FA sensing were evaluated by intracerebroventricular (ICV) administration. Food intake was assessed after 2, 4, 6, 8 and 12 h. Gene expression associated with FA sensing mechanism such as cd36, pparα and srebp1c, and neuropeptides controlling appetite such as pomca, cart, agrp2 and npy were assessed after 6 h. The ICV treatment of OA, LA and ALA activated FAT/CD36 and PPARα, rather than SA, and modulated gene expression levels of hypothalamic neuropeptides associated with appetite. And then, OA, LA and ALA inhibited food intake, which was consistent with the activation of hypothalamus FA sensing. Our data indicated some mechanisms of the hypothalamic FA sensing systems also existed in Chinese perch. It's worth noting that polyunsaturated fatty acids (PUFA) could also activate hypothalamic FA sensing mechanisms in Chinese perch. The unsaturation of FA appears to be extremely important for FA sensing mechanisms, since no major influences in Chinese perch after SA treatment. Our findings will contribute to the study of long-chain FAs sensing mechanisms in fish hypothalamus and highlight the importance of PUFAs in fish species.


Assuntos
Antígenos CD36/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos/administração & dosagem , Hipotálamo/efeitos dos fármacos , Neuropeptídeos/metabolismo , Percas/fisiologia , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Hipotálamo/metabolismo , Infusões Intraventriculares , PPAR alfa/metabolismo
6.
Chemosphere ; 238: 124609, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524604

RESUMO

Human pharmaceuticals are pollutants of special concern due to their widespread consumption over the last decades, their high persistence in the environment, and the reported alterations produced on non-target organism. The antidepressant fluoxetine (FLX) exerts its effect by inhibiting serotonin (5-HT) reuptake at the presynaptic membrane, thus increasing brain serotonergic activity. In vertebrates, there is a clear inverse relationship between hypothalamic 5-HT levels and food intake, therefore we hypothesized that FLX would inhibit food intake, and in consequence alter energy metabolism in freshwater fish. The aim of this study was to analyze the effect of FLX on feeding behavior and energy storage of the cichlid fish Cichlasoma dimerus. Adult fish were intraperitoneally injected daily with 2 or 20 µg.g-1 FLX or saline for a 5-day period, during which the 20 µg.g-1 FLX-injected fish exhibited a marked reduction in food intake, consistent with a decrease in total body weight and total hepatocyte area observed at the end of the experiment. Although not statistically significant, a marked 50% decrease in glycogen and lipid content and an increase in protein levels in liver was observed for the 20 µg.g-1 FLX dose. This was evidenced histochemically by a weak PAS positive reaction and an intense Coomasie Blue stain. Taken together, these results suggest that the SSRI antidepressant FLX produces an anorectic effect in adults of C. dimerus, which could alter normal physiological function and, in consequence, have a negative impact on fish growth, reproduction, and population success.


Assuntos
Ciclídeos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Fluoxetina/toxicidade , Inibidores de Captação de Serotonina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Fígado/metabolismo , Masculino , Reprodução/efeitos dos fármacos
7.
J Agric Food Chem ; 67(49): 13737-13750, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31789024

RESUMO

Genistein is abundant in animal feed. In this study, the side effects of high-dose genistein on intestinal health and hypothalamic RNA profile were evaluated. Chicks exposed to high-dose genistein by intraperitoneal injection (416 ± 21, 34.5 ± 2.5) and feed supplementation (308 ± 19, 27.2 ± 2.1) both showed a reduced body weight gain and feed intake in comparison with the control group (261 ± 16, 22.7 ± 1.6, P < 0.01). In comparison with the control (22.4 ± 0.5, 33.3 ± 2.4), serum levels of albumin and total protein were decreased after high-dose genistein injection (21.6 ± 0.5, 31.8 ± 1.6) and diet supplementation (20.6 ± 0.9, 29.9 ± 2.5, P < 0.001). Interestingly, the genistein diet presented the chick hypothalamus with downregulated expression of bitter receptors (TAS1R3, P < 0.05). Meanwhile, it upregulated the expressions of TAS2R1 (P < 0.05) and downstream genes (PLCB2 and IP3R3) in the ileum (P < 0.05). Accordingly, high-dose dietary genistein reduced villus height and the abundance of Lactobacillus, along with the increased abundance of pathogenic bacteria in the ileum (P < 0.05). Furthermore, transcriptomic analysis identified 348 differently expressed genes (168 upregulated and 224 downregulated) in the high-dose dietary genistein treated group in comparison with the control (P < 0.05, |log2FoldChange| > 0.585). Therefore, high-dose dietary genistein altered the hypothalamic RNA profile and signal processing. Cluster analysis further revealed that high-dose dietary genistein significantly influenced apoptosis, the immune process, and the whole synthesis of steroid hormones in the hypothalamus (P < 0.05). In conclusion, high-dose dietary genistein altered the hypothalamic RNA profile and intestinal health of female chicks.


Assuntos
Galinhas/metabolismo , Suplementos Nutricionais/efeitos adversos , Genisteína/efeitos adversos , Hipotálamo/metabolismo , RNA/genética , Ração Animal/efeitos adversos , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Genisteína/análise , Hipotálamo/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/metabolismo , RNA/metabolismo , Esteroides/metabolismo
8.
Artigo em Russo | MEDLINE | ID: mdl-31851173

RESUMO

AIM: To study an effect of cabergoline on dopamine and noradrenaline concentration and BDNF mRNA level in the rat midbrain and hypothalamus. MATERIAL AND METHODS: Twenty adult male Wistar rats were used in a single treatment paradigm: animals of the treatment group (n=10) received cabergoline (i.p., 0.5 mg/kg) and the control group (n=10) received an equivalent volume of the solvent. Quantitative analysis for the dopamine (DA) and noradrenaline (NA) was carried out using high-performance liquid chromatography (HPLC) coupled with electrochemical detection. BDNF mRNA levels were studied using quantitative RT-PCR. RESULTS AND CONCLUSION: Cabergoline significantly increases NA concentration in the midbrain 24 hours after injection: 639.2±64.5 ng/g in the treatment group versus 398.0±66.0 ng/g in the control group (p<0.05), while mean content of DA is not significantly changed (211.4±16.3 ng/g vs 169.7±54.6 ng/g, respectively). Cabergoline does not affect hypothalamic DA and NA levels. The drug increases BDNF mRNA levels by 2-times in the midbrain, but not in the hypothalamus, 24 hours after injection.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Cabergolina , Catecolaminas , Receptores de Dopamina D2 , Animais , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cabergolina/farmacologia , Catecolaminas/metabolismo , Ergolinas , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , RNA Mensageiro , Ratos , Ratos Wistar , Receptores de Dopamina D2/agonistas
9.
Int J Mol Sci ; 20(20)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614951

RESUMO

Obesity is closely associated with neuroinflammation in the hypothalamus, which is characterized by over-activated microglia and excessive production of pro-inflammatory cytokines. The present study was aimed at elucidating the effects of (-)-epigallocatechin gallate (EGCG) on palmitic acid-stimulated BV-2 microglia and high-fat-diet-induced obese mice. The results indicated the suppressive effect of EGCG on lipid accumulation, pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) release, and microglial activation in both cellular and high-fat-diet rodent models. These results were associated with lower phosphorylated levels of the janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, EGCG can attenuate high-fat-induced hypothalamic inflammation via inhibiting the JAK2/STAT3 signaling pathways in microglia.


Assuntos
Fármacos Antiobesidade/farmacologia , Catequina/análogos & derivados , Microglia/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Hipotálamo/efeitos dos fármacos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Microglia/metabolismo , Obesidade/metabolismo , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , Polifenóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Chá/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Mar Drugs ; 17(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600939

RESUMO

Leptin resistance in the hypothalamus has an essential role in obesity. Saturated fatty acids such as palmitate bind to Toll-like receptor 4 (TLR4) and lead to endoplasmic reticulum (ER) stress and leptin resistance. In this study, we evaluated whether extracts of Ecklonia cava would attenuate the ER stress induced by palmitate and reduce leptin resistance in hypothalamic neurons and microglia. We added palmitate to these cells to mimic the environment induced by high-fat diet in the hypothalamus and evaluated which of the E. cava phlorotannins-dieckol (DK), 2,7-phloroglucinol-6,6-bieckol (PHB), pyrogallol-phloroglucinol-6,6-bieckol (PPB), or phlorofucofuroeckol-A (PFFA)-had the most potent effect on attenuating leptin resistance. TLR4 and NF-κB expression induced by palmitate was attenuated most effectively by PPB in both hypothalamic neurons and microglia. ER stress markers were increased by palmitate and were attenuated by PPB in both hypothalamic neurons and microglia. Leptin resistance, which was evaluated as an increase in SOCS3 and a decrease in STAT3 with leptin receptor expression, was increased by palmitate and was decreased by PPB in hypothalamic neurons. The culture medium from palmitate-treated microglia increased leptin resistance in hypothalamic neurons and this resistance was attenuated by PPB. In conclusion, PPB attenuated leptin resistance by decreasing ER stress in both hypothalamic neurons and microglia.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Leptina/metabolismo , Neurônios/efeitos dos fármacos , Palmitatos/farmacologia , Feófitas/química , Taninos/farmacologia , Animais , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipotálamo/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , NF-kappa B/metabolismo , Neurônios/metabolismo , Obesidade/metabolismo , Floroglucinol/farmacologia , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
11.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3343-3348, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602893

RESUMO

To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Hipotálamo/efeitos dos fármacos , Neurotransmissores/química , Animais , Cromatografia Líquida , Hipotálamo/química , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
12.
Ecotoxicol Environ Saf ; 185: 109710, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31563750

RESUMO

The purpose of this research was to discuss the effects of copper (Cu)-induced toxicity on oxidative stress and autophagy in hypothalamus of broilers. In this study, 240 one-day-old broilers were randomly divided into 4 groups and the contents of dietary Cu in 4 groups were 11 mg/kg (control group), 110 mg/kg (group I), 220 mg/kg (group II), and 330 mg/kg (group III). The experiment lasted for 49 days and the hypothalamus tissues were collected for histological observation and detection of Cu content. Additionally, the indicators related to oxidative stress in hypothalamus were determined. Moreover, the mRNA expression levels of autophagy-related genes and the protein expression levels of Beclin1, LC3-II/LC3-I, and p62 in hypothalamus were measured. Results showed that the treated groups were observed vacuolar degeneration in hypothalamus compared to control group, and the Cu content in hypothalamus was increased with the increase of dietary Cu. Furthermore, the activities of SOD, CAT, T-AOC were increased in group I and group II and then decreased in group III, and the content of MDA and the mRNA levels of Nrf2, HO-1, SOD-1, CAT, GCLC, GCLM, and GST in treated groups were elevated compared to control group. Moreover, the mRNA expression levels of Beclin1, Atg5, LC3-I, LC3-II and the protein expression levels of Beclin1 and LC3-II/LC3-I up-regulated significantly with the increasing levels of Cu. However, the mRNA expression levels of p62 and mTOR and the protein expression level of p62 down-regulated remarkably. Taken together, our present study evidenced that excessive intake of Cu could induce oxidative stress and autophagy in hypothalamus of broilers.


Assuntos
Autofagia/efeitos dos fármacos , Galinhas , Cobre/toxicidade , Poluentes Ambientais/toxicidade , Hipotálamo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Galinhas/metabolismo , Cobre/metabolismo , Dieta , Exposição Dietética/análise , Relação Dose-Resposta a Droga , Poluentes Ambientais/metabolismo , Hipotálamo/metabolismo , Hipotálamo/patologia , Distribuição Aleatória
13.
Nat Commun ; 10(1): 4037, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492869

RESUMO

Increased body weight is a major factor that interferes with smoking cessation. Nicotine, the main bioactive compound in tobacco, has been demonstrated to have an impact on energy balance, since it affects both feeding and energy expenditure at the central level. Among the central actions of nicotine on body weight, much attention has been focused on its effect on brown adipose tissue (BAT) thermogenesis, though its effect on browning of white adipose tissue (WAT) is unclear. Here, we show that nicotine induces the browning of WAT through a central mechanism and that this effect is dependent on the κ opioid receptor (KOR), specifically in the lateral hypothalamic area (LHA). Consistent with these findings, smokers show higher levels of uncoupling protein 1 (UCP1) expression in WAT, which correlates with smoking status. These data demonstrate that central nicotine-induced modulation of WAT browning may be a target against human obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Nicotina/farmacologia , Receptores Opioides kappa/metabolismo , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adulto , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Estimulantes Ganglionares/administração & dosagem , Estimulantes Ganglionares/farmacologia , Humanos , Hipotálamo/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Ratos Sprague-Dawley , Receptores Opioides kappa/genética , Proteína Desacopladora 1/metabolismo
14.
Acta Diabetol ; 56(12): 1333-1339, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31506721

RESUMO

AIMS: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. METHODS: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. RESULTS: Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. CONCLUSIONS: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gliose/prevenção & controle , Hipotálamo/efeitos dos fármacos , Hipotálamo/patologia , Pioglitazona/farmacologia , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/patologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patologia , Quimioterapia Combinada , Feminino , Fluordesoxiglucose F18 , Gliose/diagnóstico , Gliose/patologia , Humanos , Hipotálamo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Sobrepeso/complicações , Sobrepeso/diagnóstico , Sobrepeso/tratamento farmacológico , Sobrepeso/patologia , Pioglitazona/administração & dosagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudo de Prova de Conceito , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/farmacologia
15.
Nutrients ; 11(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514318

RESUMO

We hypothesized that resistin is engaged in the development of leptin central insensitivity/resistance in sheep, which is a unique animal model to explore reversible leptin resistance. Thirty Polish Longwool ewes, which were ovariectomized with estrogen replacement, were used. Treatments consisted of the intravenous injection of control (saline) or recombinant bovine resistin (rbresistin): control (Control; n = 10), a low dose of rbresistin (R1; 1.0 µg/kg body weight (BW); n = 10), and a high dose of rbresistin (R2; 10.0 µg/kg BW; n = 10). The studies were performed during short-day (SD) and long-day (LD) photoperiods. Leptin and resistin concentrations were determined. Expression levels of a suppressor of cytokine signaling (SOCS)-3 and the long form of the leptin receptor (LeptRb) were determined in selected brain regions, including in the anterior pituitary (AP), hypothalamic arcuate nucleus (ARC), preoptic area (POA), and ventro- and dorsomedial nuclei (VMH/DMH). The results indicate that resistin induced a consistent decrease in LeptRb (except in POA) and an increase in SOCS-3 expression during the LD photoperiod in all selected brain regions. In conclusion, the results demonstrate that the action of resistin appears to be strongly associated with photoperiod-driven changes in the leptin signaling pathway, which may underlie the phenomenon of central leptin resistance.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Leptina/metabolismo , Adeno-Hipófise/efeitos dos fármacos , Receptores para Leptina/metabolismo , Resistina/farmacologia , Fator de Transcrição STAT3/metabolismo , Tecido Adiposo/metabolismo , Animais , Terapia de Reposição de Estrogênios , Feminino , Hipotálamo/metabolismo , Ovariectomia , Fotoperíodo , Adeno-Hipófise/metabolismo , Carneiro Doméstico , Transdução de Sinais , Fatores de Tempo
16.
Pestic Biochem Physiol ; 159: 91-97, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400790

RESUMO

The organophosphorus pesticide, triazophos (TAP) was banned to use in agriculture in several countries due to its high toxicity. However, TAP was still widely used and frequently detected in foods. Recently, many studies reported the endocrine-disrupting effect of pesticides, especially the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis. In this study, adult male Wistar rats were exposed to TAP at the dose of 0.164 and 1.64 mg/kg bodyweight (~1/500th and 1/50th of LD50) for 24 weeks and serum contents of hormones were measured. TAP exposure significantly reduced serum contents of adrenocorticotropic hormone, corticosterone and epinephrine in rats (p < .05), leading to the delay in glucose homeostasis during the insulin tolerance test and decrease in serum contents of total cholesterol, triglyceride and low density lipoprotein. Molecular docking results suggested TAP may be an antagonist of glucocorticoid receptor which decreased significantly in the liver of rats, resulting in the decreased expression of 11ß-hydroxysteroid dehydrogenase 1 and PEPCK1. This study revealed that TAP is a potential endocrine disruptor, especially in the hypothalamus-pituitary-adrenal system and may disturb the metabolism by affecting glucocorticoid receptor. This study provided new evidence about the toxicity of TAP and it was necessary to strictly control the usage of TAP in food.


Assuntos
Hipotálamo/efeitos dos fármacos , Organotiofosfatos/farmacologia , Praguicidas/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Colesterol/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Simulação de Acoplamento Molecular , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
17.
Best Pract Res Clin Endocrinol Metab ; 33(3): 101300, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31401055

RESUMO

The onset of puberty strongly depends on organizational processes taking place during the fetal and early postnatal life. Therefore, exposure to environmental pollutants such as Endocrine disrupting chemicals (EDCs) during critical periods of development can result in delayed/advanced puberty and long-term reproductive consequences. Human evidence of altered pubertal timing after exposure to endocrine disrupting chemicals is equivocal. However, the age distribution of pubertal signs points to a skewed distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon and suggests environmental influences including the possible role of nutrition, stress and endocrine disruptors. Rodent and ovine studies indicate a role of fetal and neonatal exposure to EDCs, along the concept of early origin of health and disease. Such effects involve neuroendocrine mechanisms at the level of the hypothalamus where homeostasis of reproduction is programmed and regulated but also peripheral effects at the level of the gonads or the mammary gland.


Assuntos
Disruptores Endócrinos/efeitos adversos , Puberdade/efeitos dos fármacos , Animais , Poluentes Ambientais/efeitos adversos , Feminino , Homeostase/efeitos dos fármacos , Humanos , Hipotálamo/efeitos dos fármacos , Masculino , Puberdade Precoce/epidemiologia
18.
BMC Genomics ; 20(1): 647, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412766

RESUMO

BACKGROUND: Despite the convergence of rapid technological advances in genomics and the maturing field of ecoimmunology, our understanding of the genes that regulate immunity in wild populations is still nascent. Previous work to assess immune function has relied upon relatively crude measures of immunocompetence. However, with next-generation RNA-sequencing, it is now possible to create a profile of gene expression in response to an immune challenge. In this study, captive zebra finch (Taeniopygia guttata; adult males) were challenged with bacterial lipopolysaccharide (LPS) or vehicle to stimulate the innate immune system. 2 hours after injection, birds were euthanized and hypothalami, spleen, and red blood cells (RBCs) were collected. Taking advantage of the fully sequenced genome of zebra finch, total RNA was isolated, sequenced, and partially annotated in these tissue/cells. RESULTS: In hypothalamus, there were 707 significantly upregulated transcripts, as well as 564 and 144 in the spleen and RBCs, respectively, relative to controls. Also, 155 transcripts in the hypothalamus, 606 in the spleen, and 61 in the RBCs were significantly downregulated. More specifically, a number of immunity-related transcripts (e.g., IL-1ß, RSAD2, SOCS3) were upregulated among tissues/cells. Additionally, transcripts involved in metabolic processes (APOD, LRAT, RBP4) were downregulated. CONCLUSIONS: These results suggest a potential trade-off in expression of genes that regulate immunity and metabolism in birds challenged with LPS. This finding is consistent with a hypothermic response to LPS treatment in small birds. Unlike mammals, birds have nucleated RBCs, and these results support a novel transcriptomic response of avian RBCs to immune challenge.


Assuntos
Tentilhões/genética , Tentilhões/imunologia , Perfilação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Animais , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Eritrócitos/metabolismo , Ontologia Genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
19.
Food Funct ; 10(9): 5752-5758, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31453624

RESUMO

Phloretin, abundantly present in apples, pears and other fruits, has been found to have antioxidant, immunosuppressive and anti-inflammatory activities. It has been reported that oral administration of phloretin dose-dependently increased feed intake in mice, but the mechanism is unclear yet. The aim of this study was to investigate the effect of dietary phloretin supplementation on the feed intake in C57BL/6J mice and to identify its mechanism. Here, sixty C57BL/6J mice (28-day age) were randomly chosen for four dietary treatments and fed a basal diet or a basal diet supplemented with 0.1%, 0.2%, and 0.3% phloretin, respectively, in a 6-week trial. We showed that mice in the 0.1%, 0.2%, and 0.3% phloretin-supplemented groups had increased accumulative feed intake compared with the control group. Furthermore, dietary phloretin supplementation significantly increased the ghrelin mRNA level in the stomach and hypothalamus, and decreased the cholecystokinin (CCK) mRNA level in the duodenum in a dose-dependent manner. The mRNA levels of neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin and melanocortin receptors 4 (MC4R), and pro-opiomelanocortin (POMC) in the hypothalamus were altered in response to dietary phloretin supplementation. Moreover, we confirmed that dietary phloretin supplementation reduced the expressions of miR-488 and miR-103, two feed intake-related miRNAs. Our present study provides evidence that dietary phloretin supplementation could increase feed intake in mice, which might be attributed to the stimulation of the hypothalamic feeding center via ghrelin, miRNAs (miR-103 and miR-488) and feeding signal factor-related genes (NPY, AgRP, MC4R and POMC), and to the inhibition of CCK to increase gastric emptying.


Assuntos
Suplementos Nutricionais/análise , Ingestão de Alimentos/efeitos dos fármacos , Floretina/administração & dosagem , Animais , Colecistocinina/genética , Colecistocinina/metabolismo , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Expressão Gênica/efeitos dos fármacos , Grelina/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/metabolismo
20.
Aquat Toxicol ; 214: 105240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319295

RESUMO

Fish has a strong resistance to microcystins (MCs), cyclic heptapeptide cyanotoxins, known as endocrine disrupting chemicals (EDCs) which are released during cyanobacterial blooms and many laboratory and field studies have found the hepatic recovery of fish from the MCs exposure. The aim of the present study was to investigate the recovery mechanisms of reproductive function of adult zebrafish (Danio rerio) from microcystin-LR (MC-LR) exposure. Therefore, adult female zebrafish were exposed to 0, 1 or 50 µg/L of MC-LR for 21days and transferred to MC free water for another 21 days to investigate the recovery. After MC-LR exposure, marked histological lesions in the gonads, decreased the percentage of mature oocytes, decreased number of spawned eggs, decreased fertilization and hatching rates were observed. MC-LR exposure increased the concentration of 17ß-estradiol (E2), testosterone (T) and vitellogenin (VTG) in female zebrafish. Some gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis significantly changed. The protein levels of 17ßhsd and cyp19a remarkably increased in the MC-LR exposure groups. However, our laboratory observation also indicates that zebrafish transferred from microcystin exposure to toxin-free water and reared for 21 days exhibited a nearly complete recovery of reproductive functions, including histological structure, increased the percentage of matured oocytes and spawned eggs, stable hormone levels, well-balanced transcriptional and translational levels. These results indicate that after MC-LR exposure, the reproductive impairments in zebrafish are also reversible likewise hepatic recovery seen by different studies in fish. Future studies should be conducted to explore a better understanding of the recovery mechanisms of fish from microcystins exposure.


Assuntos
Exposição Ambiental , Microcistinas/toxicidade , Reprodução/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Disruptores Endócrinos/toxicidade , Feminino , Hormônios/sangue , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/fisiologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/sangue , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
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