RESUMO
BACKGROUND/OBJECTIVES: Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. MATERIALS/SUBJECTS AND METHODS: Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR-/- mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. RESULTS: PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR-/- increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-/--BM exhibited similar adiposity gain as WT chimeras. PAFR-/- mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR-/- mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. CONCLUSIONS: Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.
Assuntos
Tecido Adiposo/fisiopatologia , Obesidade/complicações , Glicoproteínas da Membrana de Plaquetas/farmacologia , Tecido Adiposo/metabolismo , Adulto , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Paris , Receptores Acoplados a Proteínas G , Transdução de Sinais/fisiologiaRESUMO
The excessive consumption of ultra-processed foods and the development of obesity has been associated with several comorbidities, including psychiatric disorders. Excess fat tissue promotes a low-intensity inflammatory state, mainly in the white tissue, which is essential in developing metabolic alterations and influences brain homeostasis. In this scenario, Cannabidiol (CBD), a compound from Cannabis sativa, has presented anxiolytic and anti-inflammatory effects in murine models. This study verified whether CBD treatment would ameliorate the compulsive-like and anxiety-like behaviors observed after mice's chronic consumption of a high-refined carbohydrate (HC) diet. BALB/c male mice received a control or HC diet for 12 weeks followed by vehicle and CBD (30 mg/Kg, i.p.) administration, and their behavior was evaluated in the Marble Burying test (MB) and Novel Suppressing Feeding test (NSF). The sub-chronic, but not acute, treatment with CBD attenuated the compulsive-like and anxiogenic-like behavior induced by the HC diet. Our data reinforced the harmful effects of the HC diet's chronic consumption on compulsive and anxious behaviors and the potential of CBD as a drug treatment for psychiatric disorders associated with obesity.
Assuntos
Canabidiol , Camundongos , Masculino , Animais , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Camundongos Endogâmicos BALB C , Comportamento Compulsivo/induzido quimicamente , Comportamento Compulsivo/tratamento farmacológico , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , CarboidratosRESUMO
Obesity is characterized by abnormal adipose tissue expansion and is associated with chronic inflammation. Obesity itself may induce several comorbidities, including psychiatric disorders. It has been previously demonstrated that proinflammatory cytokines are able to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release, which both have a role in compulsive related behaviors. OBJECTIVE: To evaluate whether acute or chronic consumption of a high-refined carbohydrate-containing (HC) diet will modify burying-behavior in the Marble Burying Test (MBT) through augmentation of NO signaling in the striatum, a brain region related to the reward system. Further, we also verified the effects of chronic consumption of a HC diet on the reinforcing effects induced by cocaine in the Conditioned Place Preference (CPP) test. METHODS: Male BALB/c mice received a standard diet (control diet) or a HC diet for 3 days or 12 weeks. RESULTS: An increase in burying behavior occurred in the MBT after chronic consumption of a HC diet that was associated with an increase of nitrite levels in the striatum. The pre-treatment with Aminoguanidine (50â¯mg/kg), a preferential inhibitor of iNOS, prevented such alterations. Additionally, a chronic HC diet also induced a higher expression of iNOS in this region and higher glutamate release from striatal synaptosomes. Neither statistical differences were observed in the expression levels of the neuronal isoform of NOS nor in microglia number and activation. Finally, the reinforcing effects induced by cocaine (15â¯mg/kg, i.p.) during the expression of the conditioned response in the CPP test were not different between the chronically HC diet fed mice and the control group. However, HC diet-feeding mice presented impairment of cocaine-preference extinction. CONCLUSION: Altogether, our results suggest that the chronic consumption of a HC diet induces compulsive-like behavior through a mechanism possibly associated with NO activation in the striatum.
Assuntos
Comportamento Compulsivo/etiologia , Dieta da Carga de Carboidratos/efeitos adversos , Óxido Nítrico/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Carboidratos da Dieta/efeitos adversos , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Potássio/metabolismoRESUMO
OBJECTIVES: Obesity is a chronic disease frequently associated with serious co-morbidities, such as diabetes type II, metabolic syndrome, and psychiatric disorders. Little is known, however, regarding the behavioral consequences of modified diet constituents and the propensity to development of stress related disorders. Thus, the aim of this study was to verify whether chronic exposure to a normocaloric/high-carbohydrate diet will modify the animal's behavior after different stressful stimuli. METHODS: BALB/c mice were fed for 12 weeks with a standard chow diet or high refined carbohydrate-containing diet (HC). Following this period, independent groups of animals were exposed to different stress paradigms: 1 - two hours of restraint stress followed by exposure to the Elevated Plus Maze test (EPM) 24 hours later; 2 - The contextual fear conditioning (CFC) test and 3 - the tail suspension test (TST). RESULTS: Despite no change on total body weight, animals fed with HC diet showed increase in serum leptin levels and higher adiposity compared to diet control group. In behavioral tests, animals from HC diet group displayed reduction in the percentage of entries into the open arms of the EPM, evaluated 24 hours after restraint stress, suggesting an anxiogenic-like effect. It is also observed increase in aversive memory in the CFC test and depressive-like behavior in TST. DISCUSSION: Our results suggest that a moderate obesity, induced by high refined carbohydrate diet, may facilitate the development of anxiety and depressive-like behaviors after the stress. The mechanisms responsible for such effects remain to be elucidated.
Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Dieta da Carga de Carboidratos/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Estresse Psicológico , Animais , Ansiedade/etiologia , Comportamento Animal/efeitos dos fármacos , Peso Corporal , Depressão/etiologia , Dieta , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The general consensus is that milk promotes bone growth and density because is a source of calcium and contains components that enhance intestinal calcium uptake or directly affect bone metabolism. In this study, we investigated the effect of bovine-derived milk 100,000 g pellet (P100), which contains nanoparticles (<220 nm) including extracellular vesicles, on osteoclast differentiation and bone resorption. Bone marrow-derived osteoclast precursor cells were differentiated into osteoclasts by M-CSF and RANKL (control) and in the presence of milk P100. Milk P100 treatment until day 4 increased the number of TRAP-positive mononuclear cells and small (≤5 nuclei) osteoclasts. The number of large (≥6 nuclei) osteoclasts remained the same. These alterations were associated with increased expression of TRAP, NFATc1, and c-Fos. Cells seeded in a calcium-phosphate coated plate or bone slices showed reduced resorption area when exposed to milk P100 during the differentiation phase and even after osteoclast formation. Interestingly, milk P100 treatment enhanced Cathepsin K expression but reduced Carbonic Anhydrase 2 gene expression. Moreover, intracellular acid production was also decreased by milk P100 treatment. Oral delivery of milk P100 to female DBA1/J mice for 7 weeks did not alter bone area; however, increased osteoclast number and area in tibia without changes in serum RANKL and CTX-I levels. We showed for the first time the effect of milk P100 on osteoclast differentiation both in vitro and in vivo and found that milk P100 increased the formation of small osteoclasts but this does not lead to more bone resorption probably due to reduced acid secretion. J. Cell. Physiol. 232: 225-233, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Leite/metabolismo , Nanopartículas/administração & dosagem , Osteoclastos/metabolismo , Animais , Reabsorção Óssea/metabolismo , Fosfatos de Cálcio/farmacologia , Diferenciação Celular/fisiologia , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.
Assuntos
Hormônios Hipotalâmicos/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Kisspeptinas/metabolismo , Leptina/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Compostos de Trialquitina/toxicidade , Animais , Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Hormônios Hipotalâmicos/antagonistas & inibidores , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Kisspeptinas/antagonistas & inibidores , Leptina/antagonistas & inibidores , Obesidade/induzido quimicamente , Obesidade/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
PURPOSE OF REVIEW: The consumption of low-calorie beverages has increased worldwide, mainly because of their combination of sweet taste without adding significant calories to the diet. However, some epidemiological studies have linked the higher consumption of low-calorie beverages with increased body weight gain. RECENT FINDINGS: Although a matter of debate, this paradoxical association between low-calorie beverages and weight gain has been attributed to their effect on the enteral-brain axis. More specifically, artificial sweeteners present in low-calorie beverages could induce appetite increase, probably due to an ambiguous psychobiological signal (uncoupling sweet taste from calorie intake) that confounds the appetite's regulatory mechanisms, promoting overeating and, ultimately, leading to weight gain. However, many studies do not support this assumption, and the mechanisms underlying the interaction between low-calorie beverages and the enteral-brain axis remain to be defined. SUMMARY: The understanding of the effects of low-calorie drinks on the enteral-brain axis still remains in its infancy and needs to be unveiled. The consumption of low-calorie beverages reduces the calories from that drink, but compensatory phenomena may increase energy intake, and if so must be recognized and avoided.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Bebidas , Encéfalo/efeitos dos fármacos , Dieta , Ingestão de Energia/efeitos dos fármacos , Obesidade/etiologia , Edulcorantes/farmacologia , Comportamento Alimentar , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/inervação , Humanos , Hiperfagia/etiologiaRESUMO
SCOPE: Bovine milk extracellular vesicles (MEVs) have demonstrated therapeutic potential in regulating bone cell activity. However, the outcome of their use on alveolar bone loss has not yet been demonstrated. METHODS AND RESULTS: This study evaluates the effect of oral administration of MEVs on ovariectomized (OVX) mice. There is a reduced height of the alveolar bone crest in OVX mice by MEVs treatment, but the alveolar bone parameters are not altered. OVX mice are then submitted to a force-induced bone remodeling model by orthodontic tooth movement (OTM). MEVs-treated mice have markedly less bone remodeling movement, unlike the untreated OVX mice. Also, OVX mice treated with MEVs show an increased number of osteoblasts and osteocytes associated with higher sclerostin expression and reduce osteoclasts in the alveolar bone. Although the treatment with MEVs in OVX mice does not show differences in root structure in OTM, few odontoclasts are observed in the dental roots of OVX-treated mice. Compared to untreated mice, maxillary and systemic RANKL/OPG ratios are reduced in OVX mice treated with MEVs. CONCLUSION: Treatment with MEVs results in positive bone cell balance in the alveolar bone and dental roots, indicating its beneficial potential in treating alveolar bone loss in the nutritional context.
Assuntos
Perda do Osso Alveolar , Camundongos , Animais , Feminino , Humanos , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/metabolismo , Leite , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Remodelação Óssea/fisiologia , OvariectomiaRESUMO
Food intake patterns determine changes in energy expenditure due to their influence on body size and composition (percentage of fat, bone, and muscle), which can modulate signaling pathways that optimize energy consumption [...].
Assuntos
Composição Corporal , Dieta , Composição Corporal/fisiologia , Comportamento Alimentar , Metabolismo Energético/fisiologia , Ingestão de EnergiaRESUMO
BACKGROUND: Obesity leads to chronic low-grade inflammation, promoting detrimental effects on bone. The consumption of virgin coconut oil (VCO) is associated with benefits related to meta-inflammation. We evaluated the effect of VCO supplementation on osteopenia promoted by diet-induced obesity in mice. METHODS: Male BALB/c mice were fed a control (C) or highly refined carbohydrate-containing (HC) diet for eight weeks. After that, the HC diet group was supplemented with three doses of VCO for four weeks. RESULTS: The HC diet increased the adiposity and leptin levels associated with augmented systemic inflammatory cells improved with VCO supplementation. The HC diet reduced the trabecular bone in the tibia, lumbar vertebrae, distal and proximal femur, as well as the bone mineral density of the femur and alveolar bone. The VCO supplementation reverted bone osteopenia by increasing the trabecular bone in different sites and improving femur and alveolar bone microarchitecture. Although the reduced number of osteoblasts in the alveolar bone of the HC diet group was not significantly enhanced by VCO supplementation, the reduced Alp expression in the HC diet group was enhanced in the VCO group. These beneficial effects were associated with lowering the Rankl/Opg ratio. CONCLUSION: VCO supplementation might be an effective strategy to attenuate bone osteopenic effects induced by obesity.
RESUMO
OBJECTIVE: We evaluated the short-term effects of a mindfulness-based program (MBP) on weight loss through lifestyle modification in infertile women who were overweight or obese. METHODS: The participants were randomly assigned to 8 consecutive weekly sessions of MBP plus diet or diet alone. Both groups received a customized dietary plan. Body measures were taken and a questionnaire was applied to evaluate dietary habits at baseline and three months later. RESULTS: The study was completed by 28 women in the MBP group and 24 in the control group. Body weight decreased 1.8 kg (2.1%) in the MBP group (p = 0.001, follow-up vs. baseline) and 1.7 kg (1.9%) in the control group (p = 0.035). There was an average reduction of 2.9 cm of waist circumference in the MBP group (p = 0.008) and 0.3 cm in the control group (p = 0.633). There was a significant reduction in the daily energy intake of the women attending the MBP (mean difference -430 Kcal/day, p=0.010) whereas no significant change was observed in the control group. CONCLUSION: In the short term, this MBP did not affect weight loss in infertile women, but the MBP intervention contributed to reduce waist circumference, possibly due to a significant decrease in food energy intake. TRIAL REGISTRATION NUMBER: RBR-7by76r.
Assuntos
Infertilidade Feminina , Atenção Plena , Exercício Físico , Feminino , Humanos , Infertilidade Feminina/terapia , Estilo de Vida , Redução de PesoRESUMO
BACKGROUND: This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines. METHODS: Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \ groups (control, colitis, HFD and colitis + HFD). RESULTS: Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group. CONCLUSION: Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.
Assuntos
Tecido Adiposo/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/complicações , Obesidade/complicações , Adipocinas/sangue , Tecido Adiposo/irrigação sanguínea , Adiposidade , Animais , Antígenos CD/metabolismo , Quimiocinas/metabolismo , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Dieta Hiperlipídica , Epididimo/patologia , Expressão Gênica , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/patologia , Obesidade/patologia , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Studying effects of milk components on bone may have a clinical impact as milk is highly associated with bone maintenance, and clinical studies provided controversial associations with dairy consumption. We aimed to evaluate the impact of milk extracellular vesicles (mEVs) on the dynamics of bone loss in mice. MEVs are nanoparticles containing proteins, mRNA and microRNA, and were supplemented into the drinking water of mice, either receiving diet-induced obesity or ovariectomy (OVX). Mice receiving mEVs were protected from the bone loss caused by diet-induced obesity. In a more severe model of bone loss, OVX, higher osteoclast numbers in the femur were found, which were lowered by mEV treatment. Additionally, the osteoclastogenic potential of bone marrow-derived precursor cells was lowered in mEV-treated mice. The reduced stiffness in the femur of OVX mice was consequently reversed by mEV treatment, accompanied by improvement in the bone microarchitecture. In general, the RANKL/OPG ratio increased systemically and locally in both models and was rescued by mEV treatment. The number of osteocytes, as primary regulators of the RANKL/OPG system, raised in the femur of the OVX mEVs-treated group compared to OVX non-treated mice. Also, the osteocyte cell line treated with mEVs demonstrated a lowered RANKL/OPG ratio. Thus, mEVs showed systemic and local osteoprotective properties in two mouse models of bone loss reflected in reduced osteoclast presence. Data reveal mEV potential in bone modulation, acting via osteocyte enhancement and RANKL/OPG regulation. We suggest that mEVs could be a therapeutic candidate for the treatment of bone loss.
RESUMO
Consumption of poor nutrients diets is associated with fat tissue expansion and with a central and peripheral low-grade inflammation. In this sense, the microglial cells in the central nervous system are activated and release pro-inflammatory cytokines that up-regulate the inducible nitric oxide synthase (iNOS), promoting Nitric Oxide (NO) production. The excess of NO has been proposed to facilitate anxious states in humans and rodents. We evaluated whether consumption of a high-refined carbohydrate-containing diet (HC) in mice induced anxiety-like behavior in the Novelty Suppressed Feeding Test (NFST) trough facilitation of NO, in the prefrontal cortex (PFC) and hippocampus (HIP). We also verified if HC diet induces activation of microglial cells, alterations in cytokine and leptin levels in such regions. Male BALB/c mice received a standard diet or a HC diet for 3 days or 12 weeks. The chronic consumption of HC diet, but not acute, induced an anxiogenic-like effect in the NSF test and an increase in the nitrite levels in the PFC and HIP. The preferential iNOS inhibitor, aminoguanidine (50 mg/kg, i.p.), attenuated such effects. Moreover, microglial cells in the HIP and PFC were activated after chronic consumption of HC diet. Finally, the expression of iNOS in the PFC and TNF, IL6 and leptin levels in HIP were higher in chronically HC fed mice. Taken together, our data reinforce the notion that diets containing high-refined carbohydrate facilitate anxiety-like behavior, mainly after a long period of consumption. The mechanisms involve, at least in part, the augmentation of neuroinflammatory processes in brain areas responsible for anxiety control.
Assuntos
Ansiedade/metabolismo , Comportamento Animal , Carboidratos da Dieta/efeitos adversos , Inflamação/metabolismo , Tecido Adiposo/metabolismo , Animais , Ansiedade/induzido quimicamente , Modelos Animais de Doenças , Guanidinas/farmacologia , Hipocampo/metabolismo , Inflamação/induzido quimicamente , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/química , Córtex Pré-Frontal/metabolismoRESUMO
Obesity is characterized by a chronic low-grade inflammation, which has been shown to be involved in the development of comorbidities such as insulin resistance, glucose intolerance, and liver damage. Phytochemicals found in plants may modulate inflammation and improve health problems associated with the excess of adiposity. Teas prepared with many plants are used in Brazil for losing weight. In this study, we evaluated the potential of Rudgea viburnoides (Cham.) Benth. on metabolic and inflammatory disarrangement induced by high refined carbohydrate (HC)-containing diet in mice. BALB/c mice were fed with chow or HC diet for 8 weeks. After this period, the HC diet was supplemented for 4 weeks with three different doses, 40, 80, and 160 mg/kg, of crude extract of R. viburnoides. Ethanol extract at the lowest dose (40 mg/kg) reduced adipocyte size, and improved glucose tolerance and insulin sensitivity. A lower concentration of proinflammatory mediators such as tumor necrosis factor-α, interleukin-6, and CCL2 in the liver and adipose tissue, and reduced levels of cholesterol and resistin in the serum were also observed. High concentrations of chlorogenic and caffeic acids, and the flavonoids, rutin and quercetin, were confirmed by high-performance liquid chromatography/diode array detector. Therefore, these data confirm the potential of R. viburnoides leaves as nutraceutical agents for the treatment of metabolic and inflammatory changes associated with obesity.
Assuntos
Inflamação/prevenção & controle , Extratos Vegetais/farmacologia , Rubiaceae , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Carboidratos da Dieta , Suplementos Nutricionais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Obesidade Abdominal/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêutico , Folhas de PlantaRESUMO
The claimed beneficial effect of milk on bone is still a matter for debate. Recently extracellular vesicles (EVs) that contain proteins and RNA were discovered in milk, but their effect on bone formation has not yet been determined. We demonstrated previously that bovine milk-derived EVs (BMEVs) have immunoregulatory properties. Our aim was to evaluate the effect of BMEVs on osteogenesis by mice and human mesenchymal stem cells (hMSCs). Oral delivery of two concentrations of BMEVs to female DBA/1J mice during 7weeks did not alter the tibia trabecular bone area; however, the osteocytes number increased. In addition, the highest dose of BMEVs markedly increased the woven bone tissue, which is more brittle. The exposure of hMSCs to BMEVs during 21days resulted in less mineralization but higher cell proliferation. Interestingly BMEVs reduced the collagen production, but enhanced the expression of genes characteristic for immature osteoblasts. A kinetic study showed that BMEVs up-regulated many osteogenic genes within the first 4days. However, the production of type I collagen and expression of its genes (COL1A1 and COL1A2) were markedly reduced at days 21 and 28. At day 28, BMEVs again lead to higher proliferation, but mineralization was significantly increased. This was associated with increased expression of sclerostin, a marker for osteocytes, and reduced osteonectin, which is associated to bone matrix formation. Our study adds BMEVs to the list of milk components that can affect bone formation and may shed new light on the contradictory claims of milk on bone formation.
Assuntos
Matriz Óssea/metabolismo , Osteoblastos/citologia , Animais , Diferenciação Celular , Feminino , Camundongos , Camundongos Endogâmicos DBARESUMO
Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Etanercepte/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adipocinas/genética , Adipocinas/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Bovinos , Expressão Gênica , Glucose/metabolismo , Injeções Intra-Articulares , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Receptores de Interleucina-8A/antagonistas & inibidores , Receptores de Interleucina-8A/genética , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/antagonistas & inibidores , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Soroalbumina Bovina , Sulfonamidas/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.
Assuntos
Biomarcadores/urina , Diabetes Mellitus Tipo 1/imunologia , Endotélio/metabolismo , Rim/metabolismo , Fator de Necrose Tumoral alfa/urina , Adulto , Albuminúria , Biomarcadores/sangue , Cistatina C/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Interleucina-10/sangue , Interleucina-10/urina , Interleucina-6/sangue , Interleucina-6/urina , Rim/patologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules were altered in behavioral and neurological disorders. The objectives of this study were to assess neurotrophic factors levels in migraine patients in comparison with controls, and to investigate whether there was any association between them and clinical parameters. This was a cross-sectional study. We measured serum levels of neurotrophin family members - nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and 4/5 (NT3 and NT4/5) - and glial cell line-derived factor (GDNF) in patients suffering from migraine and matched controls. One hundred forty-one people were enrolled in this study, seventy-one were migraine patients and seventy were controls. Migraine patients showed more depressive and anxiety symptoms than control individuals as assessed, respectively, by the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory. Chronic and episodic migraine patients showed higher NT4/5 levels than control individuals (P=0.001). Patients with chronic migraine had lower levels of BDNF that were not influenced by the presence of depressive symptoms (P=0.02). This is the first report to evaluate NT3 and NT-4/5 levels in migraine patients. Our findings suggest a possible role of neurotrophic factors in migraine pathophysiology.