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1.
Adv Exp Med Biol ; 1131: 27-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646506

RESUMO

Ca2+, Na+ and K+- permeable ion channels as well as GPCRs linked to Ca2+ release are important drug targets. Accordingly, high-throughput fluorescence plate reader assays have contributed substantially to drug discovery efforts and pharmacological characterization of these receptors and ion channels. This chapter describes some of the basic properties of the fluorescent dyes facilitating these assay approaches as well as general methods for establishment and optimisation of fluorescence assays for ion channels and Gq-coupled GPCRs.


Assuntos
Bioensaio , Canais Iônicos , Receptores Acoplados a Proteínas-G , Animais , Bioensaio/tendências , Descoberta de Drogas , Corantes Fluorescentes/metabolismo , Humanos , Canais Iônicos/análise , Receptores Acoplados a Proteínas-G/análise
2.
Int J Cardiol ; 235: 105-113, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28284503

RESUMO

BACKGROUND: Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. METHODS: Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN. Rapid ventricular pacing of 400bpm for 4weeks was applied in HF and HF-RDN. After 4weeks, the rabbits were sacrificed and atrial myocardium were harvested for Western blot and Trichrome stain. RESULTS: The bi-atrial effective refractory period (ERP) of HF was significantly longer compared with that of control and RDN. In right atrium, the ERP of HF was also significantly longer compared with that of HF-RDN, but there was no significant difference in left atrial ERP. In bi-atrium, ion channel protein expressions of CaV1.2, NaV1.5, Kir2.1 SERCA2 and NCX were similar among 4 groups. However, the degree of atrial fibrosis was extensive in bi-atrium of HF, when compared to that of control, RDN and HF-RDN. CONCLUSION: The ERP of HF-RDN is partially shortened by RDN compared with that of HF. There are no differences ionic channel protein expressions in bi-atrium among all groups. The degree of atrial fibrosis is severe in HF, but not in HF-RDN, suggesting that RDN may regulate the atrial arrhythmogenic substrates in HF mostly through reverse structural remodeling.


Assuntos
Fibrilação Atrial , Átrios do Coração , Insuficiência Cardíaca , Simpatectomia/métodos , Animais , Fibrilação Atrial/etiologia , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial , Modelos Animais de Doenças , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Canais Iônicos/análise , Rim/inervação , Coelhos , Fibras Simpáticas Pós-Ganglionares/cirurgia
3.
PLoS One ; 11(5): e0154077, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27149380

RESUMO

BACKGROUND: The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility. METHODS: We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function. RESULTS: Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials. CONCLUSIONS: The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation.


Assuntos
Complexos Atriais Prematuros/fisiopatologia , Átrios do Coração/fisiopatologia , Canais Iônicos/fisiologia , Potenciais de Ação/fisiologia , Animais , Função Atrial/fisiologia , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/análise , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/fisiologia , Átrios do Coração/química , Canais Iônicos/análise , Canal de Potássio Kv1.4/análise , Canal de Potássio Kv1.4/fisiologia , Masculino , Camundongos , Miócitos Cardíacos/química , Miócitos Cardíacos/fisiologia , Técnicas de Patch-Clamp
4.
J Lab Autom ; 21(6): 779-793, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26702021

RESUMO

We have developed an automated patch clamp module for high-throughput ion channel screening, recording from 384 cells simultaneously. The module is incorporated into a laboratory pipetting robot and uses a 384-channel pipettor head for application of cells and compounds. The module contains 384 amplifier channels for fully parallel recordings using a digital amplifier. Success rates for completed experiments (1- to 4-point concentration-response curves for cells satisfying defined quality control parameters) of greater than 85% have been routinely achieved with, for example, HEK, CHO, and RBL cell lines expressing hNaV1.7, hERG, Kir2.1, GABA, or glutamate receptors. Pharmacology experiments are recorded and analyzed using specialized software, and the pharmacology of hNaV1.7 and hERG is described. Fast external solution exchange rates of <50 ms are demonstrated using Kir2.1. Short exposure times are achieved by stacking the external solutions inside the pipette of the robot to minimize exposure of the ligand on the receptor. This ensures that ligand-gated ion channels, for example, GABA and glutamate described in this report, can be reproducibly recorded. Stem cell-derived cardiomyocytes have also been used with success rates of 52% for cells that have a seal resistance of >200 MΩ, and recordings of voltage-gated Na+ and Ca2+ are shown.


Assuntos
Automação Laboratorial/métodos , Ensaios de Triagem em Larga Escala/métodos , Técnicas de Patch-Clamp/métodos , Animais , Linhagem Celular , Humanos , Canais Iônicos/análise , Receptores de Superfície Celular/análise , Robótica/métodos
5.
J Am Heart Assoc ; 4(12)2015 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-26656859

RESUMO

BACKGROUND: Ventricular arrhythmia is an important cause of late death in patients with repaired tetralogy of Fallot (rTOF). By using an rTOF canine model, we investigated the role of repolarization alternans and its electrophysiological mechanisms. METHODS AND RESULTS: Six dogs received right ventricular outflow tract (RVOT) transannular patch, pulmonary valve destruction, and right bundle branch ablation to simulate rTOF. After 1 year, we performed high-resolution dual-voltage and calcium optical mapping to record action potentials and calcium transients on the excised right ventricular outflow tract wedges. Another 6 dogs without operation served as control. The rTOF group was more susceptible to action potential duration alternans (APD-ALT) and spatially discordant APD-ALT than control (threshold for APD-ALT: 516±36 vs 343±36 ms; P=0.017; threshold for discordant APD-ALT: 387±30 vs 310±14 ms; P=0.046). We detected 2 episodes of ventricular tachycardia in the rTOF group, but none in the control. Expressions of Kv4.3 and KChIP2 decreased in the rTOF group. Expression of connexin 43 also decreased in the rTOF group with a corresponding decrease of conduction velocity and might contribute to spatially discordant APD-ALT. We also found distinct electrophysiological features of the RVOT, including biphasic relationship between magnitude of APD-ALT and pacing cycle length, uncoupling of APD-ALT, and calcium transients alternans, and shortened APD, but unchanged, APD restitution in rTOF. CONCLUSIONS: We demonstrated novel electrophysiological properties of the RVOT. In an rTOF model, the RVOT exhibits increased susceptibility to temporal and spatially discordant APD-ALT, which was not totally dependent on calcium transient alternans.


Assuntos
Arritmias Cardíacas/etiologia , Sistema de Condução Cardíaco/fisiopatologia , Tetralogia de Fallot/cirurgia , Animais , Arritmias Cardíacas/fisiopatologia , Conexina 43/análise , Conexinas/análise , Modelos Animais de Doenças , Cães , Eletrocardiografia , Coração/fisiopatologia , Canais Iônicos/análise , Miocárdio/química , Reação em Cadeia da Polimerase em Tempo Real , Tetralogia de Fallot/complicações , Tetralogia de Fallot/fisiopatologia
6.
Comput Biol Chem ; 58: 205-21, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26256801

RESUMO

Ion channels are integral membrane proteins that are responsible for controlling the flow of ions across the cell. There are various biological functions that are performed by different types of ion channels. Therefore for new drug discovery it is necessary to develop a novel computational intelligence techniques based approach for the reliable prediction of ion channels families and their subfamilies. In this paper random forest based approach is proposed to predict ion channels families and their subfamilies by using sequence derived features. Here, seven feature vectors are used to represent the protein sample, including amino acid composition, dipeptide composition, correlation features, composition, transition and distribution and pseudo amino acid composition. The minimum redundancy and maximum relevance feature selection is used to find the optimal number of features for improving the prediction performance. The proposed method achieved an overall accuracy of 100%, 98.01%, 91.5%, 93.0%, 92.2%, 78.6%, 95.5%, 84.9%, MCC values of 1.00, 0.92, 0.88, 0.88, 0.90, 0.79, 0.91, 0.81 and ROC area values of 1.00, 0.99, 0.99, 0.99, 0.99, 0.95, 0.99 and 0.96 using 10-fold cross validation to predict the ion channels and non-ion channels, voltage gated ion channels and ligand gated ion channels, four subfamilies (calcium, potassium, sodium and chloride) of voltage gated ion channels, and four subfamilies of ligand gated ion channels and predict subfamilies of voltage gated calcium, potassium, sodium and chloride ion channels respectively.


Assuntos
Canais Iônicos/análise , Aminoácidos/análise , Inteligência Artificial , Dipeptídeos/análise
7.
Endocr J ; 62(5): 469-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25833077

RESUMO

Miglitol is an absorbable alpha-glucosidase inhibitor that is used to control post-prandial hyperglycemia. We previously found that miglitol stimulates brown adipose tissue and prevents diet-induced obesity in mice that are fed a high-fat, high-carbohydrate diet. In this study, we examined whether miglitol can also protect against aging-dependent weight gain in mice that are fed a normal chow diet. Male C57Bl/6J mice were fed normal chow with or without miglitol (800 ppm) for 12 weeks, starting at 12 weeks of age. Food intake and body weight were monitored. After 12 weeks, adiposity, energy expenditure, and locomotor activities were measured. After sacrifice, weight of the epididymal white adipose tissue and adipocyte size were measured. Finally, Ucp1 gene expression and UCP1 protein abundance in brown adipose tissue were quantified by RT-PCR and Western analyses, respectively. Miglitol prevented age-related weight gain without affecting growth of the animals. Miglitol-treated mice showed reduced adiposity and increased oxygen consumption compared to controls, accompanied by higher UCP1 protein abundance in brown adipose tissue. Food intake and locomotor activities were not affected. These results suggest that miglitol can protect against age-dependent weight gain. Elucidating the molecular targets of miglitol in brown adipose tissue and optimizing drug delivery and efficacy may provide new strategies to combat obesity.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Tecido Adiposo Marrom/química , Envelhecimento/fisiologia , Hipoglicemiantes , Canais Iônicos/análise , Proteínas Mitocondriais/análise , Ganho de Peso/efeitos dos fármacos , 1-Desoxinojirimicina/administração & dosagem , Adiposidade/efeitos dos fármacos , Animais , Dieta , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Canais Iônicos/genética , Canais Iônicos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/fisiologia , Atividade Motora/efeitos dos fármacos , Obesidade/etiologia , Obesidade/prevenção & controle , Consumo de Oxigênio/efeitos dos fármacos , Proteína Desacopladora 1
8.
Curr Protoc Pharmacol ; 68: 11.16.1-19, 2015 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-25737155

RESUMO

Highlighted in this unit are issues that should be considered when recording glutamate receptors at the single-channel level, including some commonly encountered problems and their remedies. "UNIT 11.17, Single-Channel Analysis of Glutamate Receptors" describes analysis techniques used to characterize the recorded single-channel properties.


Assuntos
Canais Iônicos/análise , Receptores de Glutamato/análise , Linhagem Celular , Células Cultivadas , Humanos , Técnicas In Vitro/métodos , Indicadores e Reagentes/farmacologia , Técnicas de Patch-Clamp/métodos
9.
Curr Protoc Pharmacol ; 68: 11.17.1-23, 2015 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-25737156

RESUMO

This is a companion to UNIT 11.16: Single-Channel Recording of Glutamate Receptors. Described here are techniques for analyzing single-channel currents recorded from glutamate receptors to characterize their properties. In addition, issues that need to be taken into account when analyzing glutamate receptor single-channel recording results are discussed.


Assuntos
Técnicas de Química Analítica/métodos , Canais Iônicos/análise , Receptores de Glutamato/análise , Sítios de Ligação , Agonistas de Aminoácidos Excitatórios/metabolismo , Canais Iônicos/agonistas , Canais Iônicos/metabolismo , Receptores de Glutamato/metabolismo , Razão Sinal-Ruído , Software
10.
Bioconjug Chem ; 25(12): 2205-11, 2014 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-25397889

RESUMO

Immunofluorescence, a powerful technique to detect specific targets using fluorescently labeled antibodies, has been widely used in both scientific research and clinical diagnostics. The probes should be made with small antibodies and high brightness. We conjugated GFP binding protein (GBP) nanobodies, small single-chain antibodies from llamas, with new ∼7 nm quantum dots. These provide simple and versatile immunofluorescence nanoprobes with nanometer accuracy and resolution. Using the new probes we tracked the walking of individual kinesin motors and measured their 8 nm step sizes; we tracked Piezo1 channels, which are eukaryotic mechanosensitive channels; we also tracked AMPA receptors on living neurons. Finally, we used a new super-resolution algorithm based on blinking of (small) quantum dots that allowed ∼2 nm precision.


Assuntos
Microscopia de Fluorescência/métodos , Pontos Quânticos/química , Anticorpos de Domínio Único/química , Algoritmos , Membrana Celular/metabolismo , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Canais Iônicos/análise , Canais Iônicos/genética , Canais Iônicos/metabolismo , Cinesina/análise , Cinesina/metabolismo , Microscopia Eletrônica de Transmissão , Microtúbulos/metabolismo , Sondas Moleculares/química , Neurônios/metabolismo , Receptores de AMPA/análise , Receptores de AMPA/metabolismo , Anticorpos de Cadeia Única/química
11.
Cell Metab ; 20(3): 433-47, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25043816

RESUMO

Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or ß-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.


Assuntos
Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Caquexia/complicações , Neoplasias/complicações , Tecido Adiposo Marrom/imunologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Caquexia/imunologia , Caquexia/metabolismo , Caquexia/patologia , Metabolismo Energético , Humanos , Inflamação/complicações , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Canais Iônicos/análise , Camundongos , Proteínas Mitocondriais/análise , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Proteína Desacopladora 1
12.
Blood ; 123(20): e110-22, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24695852

RESUMO

Macrophages adopt an alternatively activated phenotype (AAMs) when activated by the interleukin-4receptor(R)α. AAMs can be derived either from proliferation of tissue resident macrophages or recruited inflammatory monocytes, but it is not known whether these different sources generate AAMs that are phenotypically and functionally distinct. By transcriptional profiling analysis, we show here that, although both monocyte and tissue-derived AAMs expressed high levels of Arg1, Chi3l3, and Retnla, only monocyte-derived AAMs up-regulated Raldh2 and PD-L2. Monocyte-derived AAMs were also CX3CR1-green fluorescent protein (GFP)(high) and expressed CD206, whereas tissue-derived AAMs were CX3CR1-GFP and CD206 negative. Monocyte-derived AAMs had high levels of aldehyde dehydrogenase activity and promoted the differentiation of FoxP3(+) cells from naïve CD4(+) cells via production of retinoic acid. In contrast, tissue-derived AAMs expressed high levels of uncoupling protein 1. Hence monocyte-derived AAM have properties associated with immune regulation, and the different physiological properties associated with AAM function may depend on the distinct lineage of these cells.


Assuntos
Perfilação da Expressão Gênica , Ativação de Macrófagos , Macrófagos/imunologia , Monócitos/imunologia , Animais , Antígenos CD4/análise , Proliferação de Células , Células Cultivadas , Fatores de Transcrição Forkhead/análise , Expressão Gênica , Canais Iônicos/análise , Canais Iônicos/genética , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/análise , Proteínas Mitocondriais/genética , Monócitos/citologia , Monócitos/metabolismo , Proteína Desacopladora 1
14.
Stem Cells Dev ; 23(1): 16-23, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23947933

RESUMO

Direct reprogramming of human fibroblasts into functional neurons in vitro by defined factors provides an invaluable resource for regenerative medicine. However, clinical applications must consider the risk of immune rejection, thus patient-specific induced neuronal cells (iNCs) may serve as an ideal source for autologous cell replacement. In this study, we report a robust process for functional neuronal cells from the patients' scalp by lentiviral gene delivery of Ascl1, Myt1l, and Sox2. These three-factor iNCs are similar to human neuronal cells in morphology, surface antigens, gene expression, and electrophysiological characteristics. Our findings might provide a source of patient-specific functional neurons for cell therapy.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Reprogramação Celular/genética , Fibroblastos/fisiologia , Células-Tronco Neurais/fisiologia , Neurônios/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Lesões Encefálicas/terapia , Diferenciação Celular , Transformação Celular Neoplásica , Células Cultivadas , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Humanos , Ativação do Canal Iônico , Canais Iônicos/análise , Camundongos , Camundongos SCID , Regeneração Nervosa , Proteínas do Tecido Nervoso/genética , Fatores do Domínio POU/genética , Fatores de Transcrição SOXB1/genética , Pele/citologia , Fatores de Transcrição/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-23576958

RESUMO

Most neuron types possess elaborate dendritic arbors that receive and integrate excitatory and inhibitory inputs from numerous other neurons to give rise to cell-type specific firing patterns. The computational properties of these dendrites are therefore crucial for neuronal information processing, and are strongly determined by the expression of many types of voltage-gated ion channels in their membrane. The dendritic distribution patterns of these ion channels are characteristic for each ion channel type, are dependent on the neuronal identity, and can be modified in a plastic or pathophysiological manner. We present a method that enables us to semi-automatically map and quantify in 3D the expression levels of specific ion channel types across the entire dendritic arbor. To achieve this, standard immunohistochemistry was combined with reconstruction and quantification procedures for the localization and relative distribution of ion channels with respect to dendritic morphology. This method can, in principle, be applied to any fluorescent signal, including fluorescently tagged membrane proteins, RNAs, or intracellular signaling molecules.


Assuntos
Dendritos/química , Dendritos/fisiologia , Imagem Tridimensional/métodos , Canais Iônicos/análise , Canais Iônicos/fisiologia , Animais , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/química , Neocórtex/citologia , Neocórtex/fisiologia , Gravidez
16.
Biotechniques ; 54(4): 191-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23581465

RESUMO

Plasma membrane receptors, transporters, and ion channel molecules are often found as oligomeric structures that participate in signaling cascades essential for cell survival. Different states of protein oligomerization may play a role in functional control and allosteric regulation. Stochastic GFP-photobleaching (SGP) has emerged as an affordable and simple method to determine the stoichiometry of proteins at the plasma membrane. This non-invasive optical approach can be useful for total internal reflection of fluorescence microscopy (TIRFM), where signal-to-noise ratio is very high at the plasma membrane. Here, we report an alternative methodology implemented on a standard laser scanning confocal microscope (LSCM). The simplicity of our method will allow for its implementation in any epifluorescence microscope of choice.


Assuntos
Membrana Celular/química , Proteínas de Fluorescência Verde/análise , Proteínas de Membrana/análise , Microscopia Confocal/métodos , Células HEK293 , Humanos , Canais Iônicos/análise , Fotodegradação
17.
Lipids ; 48(5): 481-95, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23417844

RESUMO

We aimed to assess the effects of maternal supplementation with the main fat sources used in the human Western diet (olive oil, butter, margarine) on milk FA composition and on plasma FA profile of offspring, and to determine whether it may influence body-weight-gain (BWG) and adiposity of offspring during the suckling period. Wistar rats were supplemented with the different fat sources from day 14 of gestation and throughout lactation. Olive oil-supplemented dams showed the highest proportion of oleic-acid in milk, with no changes in plasma. Their offspring also showed the highest proportion of this FA in plasma, lower BWG during the suckling period, and higher levels of UCP1 in brown adipose tissue (BAT) at weaning. Margarine-supplemented dams showed the highest percentage of PUFA in milk, and a similar tendency was found in plasma of their offspring. Butter-supplemented dams displayed higher proportion of saturated FA (SFA) in milk compared to other fat-supplemented dams, but lower than controls. Control offspring also showed higher proportion of SFA in plasma and greater BWG during the suckling period than fat-supplemented groups. Significant correlations were found between the relative content of some milk FA and BWG of offspring, in particular, oleic-acid levels correlated negatively with BWG and positively with UCP1 levels. These results show that maternal dietary source of fat affects milk FA composition and circulating FA profile, as could be expected, but also BWG and thermogenic capacity of offspring during the suckling period. An effect of oleic-acid stimulating BAT thermogenic capacity of suckling pups is proposed.


Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos/análise , Ácidos Graxos/sangue , Leite/metabolismo , Ganho de Peso , Tecido Adiposo Marrom/química , Tecido Adiposo Marrom/metabolismo , Animais , Animais Lactentes , Ácidos Graxos/metabolismo , Feminino , Canais Iônicos/análise , Canais Iônicos/metabolismo , Lactação , Masculino , Leite/química , Proteínas Mitocondriais/análise , Proteínas Mitocondriais/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/análise , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Proteína Desacopladora 1
20.
BMJ Case Rep ; 20122012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22914232

RESUMO

A hibernoma is a benign tumour of brown adipose tissue (BAT). BAT is also present in physiological depots, previously considered residual. However, in 2009 functional BAT in adults was reported. Metabolically active BAT is suggested to significantly influence the energy balance and increasing BAT activity could possibly treat obesity. This strongly increased the interest in BAT in man and currently more research is conducted. We describe the case of an intramuscular hibernoma and illustrate the pathophysiology of the observed hibernoma in relation to recent insights on physiological BAT. Immunofluorescence staining of the hibernoma showed the presence of uncoupling-protein-1, a protein specific for active BAT. This suggests that this hibernoma contains BAT that could possibly contribute to the human energy balance.


Assuntos
Tecido Adiposo Marrom/metabolismo , Lipoma/patologia , Neoplasias Musculares/patologia , Tecido Adiposo Marrom/química , Nádegas , Metabolismo Energético , Humanos , Canais Iônicos/análise , Lipoma/química , Lipoma/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/análise , Neoplasias Musculares/química , Neoplasias Musculares/cirurgia , Tomografia Computadorizada por Raios X , Proteína Desacopladora 1
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