Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice.

OBJECTIVES: Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. METHODS: Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. RESULTS: In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480- was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. CONCLUSIONS: These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.

Mechanisms underlying fat pad remodeling induced by fasting: role of PAF receptor.

OBJECTIVES: Fasting has long been practiced for political and religious reasons and to lose weight. However, biological responses during fasting have yet to be fully understood. Previous studies have shown that cytokines may control fat pad expansion, at least in part, owing to the induction of lipolysis. Indeed, we have previously shown that mice with a lower inflammatory response, such as platelet-activating factor receptor knockout mice (PAFR-/-), are prone to gain weight and adiposity. The aims of this study were to determine whether adipose tissue becomes inflamed after fasting and to evaluate whether the PAF signaling is a factor in the fat loss induced by fasting. METHODS: Wild-type (WT) and PAFR-/- mice were fasted for 24 h. Adiposity, leukocyte recruitment, and cytokine levels were evaluated. Multiple comparisons were performed using two-way analysis of variance and post hoc Fisher exact test. RESULTS: After fasting, male WT mice showed lower adiposity (P < 0.001), higher recruitment of immune cells (P < 0.001), and increased cytokine levels (P < 0.05) in adipose tissue. Although WT mice lost ~79% of their adipose tissue mass, PAFR-/- mice lost only 36%. Additionally, PAFR-/- mice did not show enhanced cytokine and chemokine levels after fasting (P > 0.05). CONCLUSION: Despite low-grade inflammation being associated with metabolic syndrome, at least in part, the inflammatory milieu is also important to induce proper fat mobilization and remodeling of adipose tissue.

Role of adipose tissue inflammation in fat pad loss induced by fasting in lean and mildly obese mice.

Inflammation induced by obesity contributes to insulin resistance and atherosclerosis. Indeed, high levels of proinflammatory cytokines trigger chronic low-grade inflammation and promote detrimental metabolic effects in the adipose tissue. On the other hand, inflammation seems to control fat pad expansion and to have important functions on lipolysis and glucose metabolism. Thus, it is possible that inflammation may also drive fat pad loss, as seen during long-fast periods. Herein, we have used fasting as a strategy to induce weight loss and evaluate the possible role of inflammation on adipose tissue remodeling. Male BALB-c mice were fed with chow diet (lean mice) or with high-carbohydrate refined diet (mildly obese mice) for 8 weeks. After that, animals were subjected to 24 h of fasting. There was a 63% reduction of adiposity in lean mice following fasting. Furthermore, the adipose tissue was enriched of immune cells and had a higher content of IL-6, TNF-alpha, IL-10, TGF-ß and CXCL-1. Interestingly, mildly obese mice, subjected to the same 24-h fasting period, lost only 33% of their adiposity. Following fasting, these mice did not show any increment in leukocyte recruitment and cytokine levels, as did lean mice. Our findings indicate that inflammation participates in fat mass loss induced by fasting. Although the chronic low-grade inflammation seen in obesity is associated with metabolic diseases, a lower inflammatory response triggered by fasting in mildly obese mice impairs fat pad mobilization.

Hypometabolism as a potential risk factor for overweight and obesity in liver recipients.

OBJECTIVE: The aim of the present study was to identify whether overweight liver recipients are hypometabolic. METHODS: Liver transplantation (LT) recipients (n = 20), who were 18 to 65 y of age, had a body mass index (BMI) ≥25 kg/m2, and were 1 to 3 y post-transplant. They were matched with healthy controls in terms of sex, age, BMI, and body composition. Dietary intake data were collected using a 3-d food record. The individuals' daily activities were converted into metabolic equivalents. Resting energy expenditure (REE) was assessed in the morning after an overnight fast (12 h), by indirect calorimetry, using an open-circuit calorimeter. RESULTS: Total energy and macronutrient intakes were similar among liver recipients and controls. The majority of the individuals from both groups were sedentary (75%; n = 15/group). Patients who underwent LT showed lower REE (1449.15 ± 101.25 kcal) compared with the control group (1768.45 ± 86.94 kcal). Likewise, the ratio of REE to fat-free mass (FFM) was lower in the LT group (28.9 ± 1.7 kcal/ kg) than in the control group (32.9 ± 0.9 kcal/ kg; P < 0.05). The correlation between the FFM and the REE was strong in control participants (r = 0.73; P < 0.01), whereas it was moderate in the LT group (r = 0.45). CONCLUSION: The REE of overweight liver recipients is reduced and it might be a risk factor for excessive body weight gain in this population.

Double-blind placebo-controlled randomized clinical trial of ginger ( Zingiber officinale Rosc.) addition in migraine acute treatment.

BACKGROUND: Previous studies have demonstrated the analgesic effects of ginger in different conditions, but evidence about its efficacy in migraine treatment is scarce. OBJECTIVE: This study aimed to evaluate the potential of ginger to improve acute migraine as an add-on strategy to standard treatment. METHODS: A double-blind placebo-controlled randomized clinical trial in the emergency room of a general hospital was conducted. Patients who sought medical care at the time of migraine attack were enrolled in this study. Only adults with episodic migraine (one to six migraine attacks per month) with or without aura were included. Sixty participants were randomized into two groups in which they received 400 mg of ginger extract (5% active ingredient) or placebo (cellulose), in addition to an intravenous drug (100 mg of ketoprofen) to treat the migraine attack. Patients filled a headache diary before, 0.5 h, 1 h, 1.5 h and 2 h after the medication. Pain severity, functional status, migraine symptoms and treatment satisfaction were also recorded. RESULTS: Patients treated with ginger showed significantly better clinical response after 1 h ( p = 0.04), 1.5 h ( p = 0.01) and 2 h ( p = 0.04). Furthermore, ginger treatment promoted reduction in pain and improvement on functional status at all times assessed. CONCLUSIONS: The addition of ginger to non-steroidal anti-inflammatory drugs may contribute to the treatment of migraine attack. This trial is registered at ClinicalTrials.gov (NCT02568644).

Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice.

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

Virgin coconut oil is effective to treat metabolic and inflammatory dysfunction induced by high refined carbohydrate-containing diet in mice.

The global rise in obesity rates is alarming since this condition is associated with chronic low-grade inflammation and secondary comorbidities as glucose intolerance, cardiovascular disease and liver damage. Therefore, a lot of dietary approaches are proposed to prevent and to treat obesity and its associated disorders. Virgin coconut oil (VCO) is well known as a functional food due to its significant amounts of medium-chain triglycerides. This study aimed to evaluate the effect of VCO on adiposity, metabolic and inflammatory dysfunctions induced by a high-refined carbohydrate-containing (HC) diet in mice. Male BALB/c mice were divided into two groups and fed with control (C) or HC diet to induce obesity for eight weeks. At the 9th week mice fed with HC diet were randomly regrouped into four groups, and were kept this way until the 12th week, as following: (i) HC diet alone or HC diet supplemented with three different VCO doses (ii) 1000 mg/kg, (iii) 3000 mg/kg and (iv) 9000 mg/kg. Regardless of the concentration used, VCO supplementation promoted lower adiposity and also improvement in glucose tolerance, lower serum glucose and lipid levels and decreased hepatic steatosis. Moreover, VCO intake induced a lower inflammatory response due to decreased number of leukocytes and TNF-α and IL-6 concentrations in adipose tissue, as well as reduced counts of total leukocytes, mononuclear and polymorphonuclear circulating cells. Our data showed that VCO can be considered as an interesting potential dietary approach to attenuate obesity and its metabolic and inflammatory alterations.

Paradoxical role of tumor necrosis factor on metabolic dysfunction and adipose tissue expansion in mice.

OBJECTIVES: Tumor necrosis factor (TNF) is a well-known cytokine that triggers insulin resistance during obesity development. On the other hand, it is also known that TNF induces a fat mass loss during acute diseases. However, whether TNF has a protective and physiological role to control adipose tissue expansion during obesity still needs to be verified. The aim of this study was to evaluate whether the ablation of TNF receptor 1 (TNFR1) alters fat mass and insulin resistance induced by a highly refined carbohydrate-containing (HC) diet. METHODS: Male C57 BL/6 wild-type (WT) mice and TNFR1 knockout (TNFR1-/-) mice were fed with chow or with the HC diet for 16 wk. RESULTS: TNFR1-/- mice gained more body weight than the WT groups independent of the diet composition. TNFR1-/- mice fed with the chow diet showed higher adiposity, accompanied by higher serum leptin levels. However, these mice showed lower non-esterified fatty acid levels. Furthermore, TNFR1-/- mice had suppressed TNF, interleukin (IL)-6, and IL-10 levels in adipose tissue compared with WT mice. TNFR1-/- mice fed with the HC diet were protected from increased adiposity and glucose intolerance induced by the HC diet and exhibited lower serum resistin levels. CONCLUSIONS: TNF signaling appears to have a paradoxical role on metabolism. Ablation of TNFR1 leads to a reduction of inflammatory cytokines in adipose tissue that is accompanied by higher adiposity in mice fed with chow diet. However, when these mice are given the HC diet, the loss of TNFR1 improves insulin sensitivity and protects mice against additional fat mass.

Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation.

OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known about the acute inflammatory response in joints that results from diet-induced adipose tissue remodeling. The objective of this study was to determine whether alterations in adipose tissue mass arising from food consumption modify the inflammatory response of antigen-induced joint inflammation in mice. METHODS: Male BALB/c mice were fed a chow diet, a highly refined carbohydrate-containing (HC) diet for 8 wk. They were then immunized and, after 2 wk, received a knee injection of methylated bovine serum albumin (mBSA). They were sacrificed at 6, 24, and 48 h after injection. The effect of the cafeteria diet for 8 wk, which also increases adipose tissue, or conjugated linoleic acid (CLA) supplementation for 4 wk, a model of lipodystrophy, was evaluated 24 h after knee challenge with mBSA. RESULTS: Cellular influx, predominantly neutrophils, in synovial fluid was attenuated in the HC diet group, as were levels of myeloperoxidase and IL-1ß in periarticular tissue and histopathological analysis. These responses were associated with reduced adiponectin and increased leptin in serum, which was pronounced in mice fed the HC diet. Cafeteria diet and CLA supplementation induced a profile similar to that seen with the HC diet in terms of inflammation, disease response, and metabolic alteration. Interestingly, after the injection of mBSA, the area of adipocytes in the infrapatellar fat pad increased in mice fed with chow diet similar to those fed the HC and cafeteria diet. CONCLUSIONS: We demonstrated that attenuation of joint response induced by diet was independent of adipose tissue remodeling but could be associated with metabolic alterations.

Acute intake of a high-fructose diet alters the balance of adipokine concentrations and induces neutrophil influx in the liver.

The postprandial state is a period of metabolic fluxes, biosynthesis and oxidative metabolism. A considerable amount is known about the inflammatory response to the chronic consumption of fructose, but little is known about its effects in the postprandial state. The aim of the present study was to investigate the inflammatory effects of a single meal containing fructose on healthy mice. Male BALB/c and LysM-eGFP mice at 12-14 weeks were divided into three groups: fasted, control (mice fed with a sucrose-containing diet) and fructose (mice fed with a fructose-containing diet). One, 2 or 4 h postprandial, the BALB/c mice were killed, and samples were collected. LysM-eGFP mice were submitted to intravital microscopy. The fed mice showed a low-grade inflammatory response apart from dietary composition, which was characterized by increased numbers of leukocytes and high serum concentrations of pentraxin 3, leptin and resistin. TNF-α and CCL2 concentrations rose in the liver after the meal. IL-6 concentration increased and IL-10 decreased in the adipose tissue of the fed mice. Mice fed with the fructose-containing diet showed an intensification of the inflammatory response. Furthermore, the adiponectin concentration dropped, and the liver influx of neutrophils increased after fructose intake. Overall, this study showed a rapid increase in the systemic and tissue-specific immune response after a balanced meal. The study also showed an increased neutrophil influx in liver associated with an imbalance of adipokine concentrations and an increase of cytokine in the liver and adipose tissue following a fructose-containing meal.

Capacitação dos agentes comunitários de saúde em aleitamento materno e alimentação complementar no âmbito da atenção primária, em Belo Horizonte, Minas Gerais / Community health Worker training on breastfeeding and complementary feeding in the context of primary health care in Belo Horizonte, Minas Gerais

Trata-se de um relato de experiência sobre a capacitação dos Agentes Comunitários de Saúde em Aleitamento Materno e Alimentação Complementar, focando na metodologia participativa e na análise qualitativa dos resultados. O trabalho teve como objetivo a incorporação de novas práticas pelos profissionais sobre educação em saúde e, portanto, a aproximação do paciente e do profissional. Participaram das discussões quatorze profissionais, subdivididos em dois grupos. Os resultados obtidos foram positivos, uma vez que houve participação ativa dos profissionais por meio da exposição de dúvidas com relação às práticas comumente adotadas pelas mães atendidas na unidade, com relatos de vivências e dificuldades diárias. Ressalta-se a importância dessa capacitação para a comunidade local, tendo em vista que a interação e a troca de saberes entre profissionais e a comunidade enriquece e modifi ca o perfil dos profissionais ao aproximar os usuários das unidades de saúde e possibilitar o atendimento integral à saúde.

We report an experience concerning the training of Community Health Professionals about breastfeeding and complementary feeding, focusing on participatory methodology and qualitative analysis. The aim of the study was the incorporation of new professional practices concerning health education, and thus, the improvement of the relationship between patient and professional. Fourteen health workers were divided into two groups and participated in the discussions. The results were positive, since there was active participation by the professionals, in airing doubts about the practices commonly adopted by mothers in the community and reports about experiences and daily problems. It is important to emphasize the value of this training for the local community, considering that the interaction and exchange of knowledge between professionals and community enrich and modify the visibility of professionals, by approaching the community and enabling comprehensive health care.

Perfil peptídico de hidrolisados enzimáticos do concentrado proteico do soro de leite, obtidos pela ação da pancreatina e da papaína / Peptide profile of enzymatic hydrolysates from whey protein concentrate obtained by action of pancreatin and papain

The aim of this study was to obtain enzymatic hydrolysates from whey protein concentrate with high oligopeptide, especially di- and tripeptides, and free amino acid contents, besides small amounts of large peptides. Different parameters were evaluated such as type of enzyme (pancreatin and papain), enzyme:substrate ratio (0.5:100, 1:100, 2:100 and 3:100), and the use of ultrafi ltration. The peptide profi les of the hydrolysates were characterized by using a fractionation method by size-exclusion HPLC followed by a rapid Corrected Fraction Area method for quantifying the components of the chromatographic fractions. The results showed that, in terms of number of analyzed samples, the pancreatin action was more advantageous than papain. However, the best peptide profile was obtained by papain, reaching 15.29% of di- and tripeptides, 47.83% of free amino acids and 25.73% of large peptides. The use of the smallest enzyme:substrate ratio (0.5:100) was beneficial in some cases for both enzymes, while the lack of ultrafiltration was favorable just for pancreatin.

El objetivo de este trabajo fue obtener hidrolizados enzimáticos a partir de concentrado proteico de suero lácteo con elevados contenidos de oligopéptidos, especialmente di y tri péptidos, y aminoácidos libres, además de reducida cantidad de grandes péptidos. Para eso fueron evaluados algunos parámetros como el tipo de enzima (pancreatina o papaína), la relación enzima:substrato (0,5:100, 1:100, 2:100 y 3:100)y el empleo de ultrafiltración. Para evaluar el perfil peptídico, los hidrolizados se sometieron a fraccionamiento en cromatografía líquida de alta eficiencia de exclusión molecular (SE-HPLC) y para la cuantificación de los componentes de las fracciones de la cromatografía fue utilizado el método del Área Corregida de la Fracción (ACF). Los resultados indican que el uso de pancreatina fue más ventajoso que el de papaína, así como la menor relación enzima:substrato (0,5:100). Por otro lado, el mejor perfil peptídico (15,29% de di y tripéptidos, 47,83% de aminoácidos libresy 25,73% de grandes péptidos) fue conseguido con el empleo de papaína. La menor relación enzima:substrato (0,5:100) fue favorable en algunos casos para las dos enzimas. La ausencia de ultrafiltración favoreció los hidrolizados producidos con pancreatina.

O presente trabalho teve como objetivo a obtenção de hidrolisados enzimáticos do concentrado proteico do soro de leite com elevado teor de oligopeptídeos, principalmente di- e tripeptídeos, e de aminoácidos livres, além de quantidade reduzida de grandes peptídeos. Para tal, foram avaliados diferentes parâmetros, como tipo de enzima (pancreatina e papaína), relação enzima:substrato (0,5:100, 1:100, 2:100 e 3:100) e o emprego da ultrafiltração. Caracterizou-se o perfil peptídico pelo fracionamento dos hidrolisados por cromatografia líquida de alta eficiência de exclusão molecular e, para a quantificação dos componentes das frações cromatográficas, empregou-se o método rápido da Área Corrigida da Fração. Os resultados obtidos indicaram que, em termos de número de casos analisados, a ação da pancreatina foi mais vantajosa do que a da papaína. Entretanto, o melhor perfil peptídico foi obtido pela açãoda papaína, dando origem a 15,29% de di- e tripeptídeos, 47,83% de aminoácidos livres e 25,73% de grandes peptídeos. A utilização da menor relação enzima:substrato (0,5:100) foi benéfica em alguns casos para ambas as enzimas, enquanto que a ausência da ultrafiltração mostrou-se favorável apenas para a pancreatina.

Valor diagnóstico da punçäo-biópsia pleural: experiência em um serviço de clínica médica / Efficacy of thoracentesis and pleura biopsy in the diagnosis of pleural inflamatory diseases: experience in an internal medicine ward

OBJETIVO: Avaliar o valor da punçäo-biópsia pleural no diagnóstico das doenças inflamatórias da pleura. MÉTODO: Foi feito um estudo retrospectivo de 82 toracocenteses realizadas durante um período de 42 meses em uma enfermaria de clínica médica no Rio de Janeiro. Os aspectos bioquímico, citológico e bacteriológico do líquido pleural e o exame histopatológico do fragmento pleural foram correlacionados com o diagnóstico final. A sensibilidade e os valores preditivos da concentraçäo protéica e da percentagem de linfócitos no líquido pleural foram calculados utilizando diferentes valores de corte. RESULTADOS: Dos 82 pacientes, 73 (89 por cento) tinham tuberculose. Todos os pacientes com menos de 35 anos tinham tuberculose. O valor preditivo negativo para o diagnóstico de tuberculose aumentou de 17,1 por cento para 66,7 por cento utilizando 4,5g/dL e 2,5g/dL, respectivamente, como valores de corte para a concentraçäo de protéina no líquido pleural. O valor preditivo positivo, de 94,2 por cento. A pesquisa de BAAR no líquido pleural foi negativa nas 82 amostras. A sensibilidade do exame histopatológico da pleura foi de 69,2 por cento para o diagnóstico de tuberculose. CONCLUSÄO: A tuberculose foi a causa mais comum de derrame pleural em todos as faizas etárias. O exame que mais contribuiu para confirmar este diagnóstico foi a análise histopatológica. Os autores sugerem que a punçäo pleural e a biópsia sejam realizadas simultaneamente nas populaçöes em que a tuberculose tenha alta prevalência