Maria do Carmo Gouveia Peluzio

Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia

Lipopolysaccharide (LPS) may play an important role in chronic diseases through the activation of inflammatory responses. The type of diet consumed is of major concern for the prevention and treatment of these diseases. Evidence from animal and human studies has shown that LPS can diffuse from the gut to the circulatory system in response to the intake of high amounts of fat. The method by which LPS move into the circulatory system is either through direct diffusion due to intestinal paracellular permeability or through absorption by enterocytes during chylomicron secretion. Considering the impact of metabolic diseases on public health and the association between these diseases and the levels of LPS in the circulatory system, this review will mainly discuss the current knowledge about high-fat diets and subclinical inflammation. It will also describe the new evidence that correlates gut microbiota, intestinal permeability and alkaline phosphatase activity with increased blood LPS levels and the biological effects of this increase, such as insulin resistance. Although the majority of the studies published so far have assessed the effects of dietary fat, additional studies are necessary to deepen the understanding of how the amount, the quality and the structure of the fat may affect endotoxaemia. The potential of food combinations to reduce the negative effects of fat intake should also be considered in future studies. In these studies, the effects of flavonoids, prebiotics and probiotics on endotoxaemia should be investigated. Thus, it is essential to identify dietetic strategies capable of minimising endotoxaemia and its postprandial inflammatory effects.

Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis

Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyers patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyers patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

Potential mechanisms for the emerging link between obesity and increased intestinal permeability

Recently, increased attention has been paid to the link between gut microbial composition and obesity. Gut microbiota is a source of endotoxins whose increase in plasma is related to obesity and insulin resistance through increased intestinal permeability in animal models; however, this relationship still needs to be confirmed in humans. That intestinal permeability is subject to change and that it might be the interface between gut microbiota and endotoxins in the core of metabolic dysfunctions reinforce the need to understand the mechanisms involved in these aspects to direct more efficient therapeutic approaches. Therefore, in this review, we focus on the emerging link between obesity and increased intestinal permeability, including the possible factors that contribute to increased intestinal permeability in obese subjects. We address the concept of intestinal permeability, how it is measured, and the intestinal segments that may be affected. We then describe 3 factors that may have an influence on intestinal permeability in obesity: microbial dysbiosis, dietary pattern (high-fructose and high-fat diet), and nutritional deficiencies. Gaps in the current knowledge of the role of Toll-like receptors ligands to induce insulin resistance, the routes for lipopolysaccharide circulation, and the impact of altered intestinal microbiota in obesity, as well as the limitations of current permeability tests and other potential useful markers, are discussed. More studies are needed to reveal how changes occur in the microbiota. The factors such as changes in the dietary pattern and the improvement of nutritional deficiencies appear to influence intestinal permeability, and impact metabolism must be examined. Also, additional studies are necessary to better understand how probiotic supplements, prebiotics, and micronutrients can improve stress-induced gastrointestinal barrier dysfunction and the influence these factors have on host defense. Hence, the topics presented in this review may be beneficial in directing future studies that assess gut barrier function in obesity.

Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors

BACKGROUND & AIMS Altered intestinal permeability has been shown to be associated with metabolic alterations in animal models of obesity, but not in humans. The aim of this study was to assess intestinal permeability in obese women and verify if there is any association with anthropometric measurements, body composition or biochemical variables. METHODS Twenty lean and twenty obese females participated in the study. Anthropometric measurements, body composition and blood pressure were assessed and biochemical analyses were performed. Administration of lactulose and mannitol followed by their quantification in urine was used to assess the intestinal permeability of volunteers. RESULTS The obese group showed lower HDL (p < 0.05), higher fasting glucose, insulin, HOMA index and lactulose excretion than the lean group (p < 0.05), suggesting increased paracellular permeability. Lactulose excretion showed positive correlation (p < 0.05) with waist and abdominal circumference. Blood insulin and the HOMA index also increased with the increase in mannitol and lactulose excretion and in the L/M ratio (p < 0.05). L/M ratio presented a negative correlation with HDL concentration (p < 0.05). CONCLUSIONS We demonstrated that intestinal permeability parameters in obese women are positively correlated with anthropometric measurements and metabolic variables. Therapeutic interventions focused on intestine health and the modulation of intestinal permeability should be explored in the context of obesity.

Nutrição e doenças cardiovasculares: os marcadores de risco em adultos

As doencas cardiovasculares contribuem significativamente, como grupo causal, para a taxa de mortalidadeem todas as regioes brasileiras, principalmente na Regiao Sudeste. Alem disso, constituem uma das principaiscausas de permanencia hospitalar prolongada e sao responsaveis pela principal alocacao de recursos publicosem hospitalizacoes no Brasil. O onus economico das doencas cardiovasculares tem crescido exponencialmentenas ultimas decadas. O risco de se desenvolver doenca cardiovascular e avaliado com base na analise conjuntade caracteristicas que aumentam a chance do individuo vir a apresentar a doenca. O conhecimento dessesfatores associados ao risco e de grande importância para o estabelecimento de estrategias de prevencao. Esteartigo em questao revisa os principais marcadores de risco para doencas cardiovasculares em adultos,relacionados a nutricao, como os antropometricos, dieteticos e bioquimicos. Alem disso, enfatiza o impactodestas morbidades na sociedade, bem como a necessidade de serem estabelecidas medidas de prevencaoprimaria no controle das mesmas.

Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors

SCFA provide energy to the host and influence lipid and glucose metabolism, suggesting that they may have an impact on the occurrence of metabolic risk factors. The aim of the present study was to determine the concentration of SCFA in faeces of lean and obese individuals and to analyse whether associations between faecal SCFA and metabolic syndrome parameters are present. Lean (n 20) and obese (n 20) women of similar age (28·5 (sd 7·6) v. 30·7 (sd 6·5) years, P= 0·33) participated in the study. Anthropometric measurements, body composition, blood pressure and biochemical parameters were assessed. SCFA were extracted from faeces and quantified by GC. Blood pressure and blood glucose, although within the normal limits, were higher in the obese group compared to lean subjects (P< 0·05). Lower HDL concentration and higher insulin and homeostasis model assessment (HOMA) index were observed in the obese than in the lean group (P< 0·05). The median values of SCFA (% w/w) from the lean and obese groups were butyric (0·021 v. 0·044, P= 0·024), propionic (0·021 v. 0·051, P= 0·007) and acetic (0·03 v. 0·061, P= 0·01). SCFA correlated positively with metabolic syndrome risk factors such as adiposity, waist circumference and HOMA index (P< 0·05), and inversely with HDL (P< 0·05). Our results suggest that the higher faecal concentration of SCFA is associated with metabolic risk factors and thus may influence metabolic homeostasis.

Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats

This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)‐induced extra‐pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ‐induced extra‐pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.

Red but not white meat consumption is associated with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men

Background The influence of diet on metabolic syndrome and oxidative stress are not completely known. Design This cross-sectional study assessed the association of red meat and white meat consumption with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men. Methods A total of 296 subjects (age: 50.5 ± 5.0 years, body mass index: 25.8 ± 3.5 kg/m2) were evaluated. Anthropometry, lifestyle features, blood biochemical parameters, diagnosis of metabolic syndrome, homeostatic model assessment for insulin resistance, a lipid peroxidation marker (oxidized low-density lipoprotein) and triglycerides:high-density lipoprotein cholesterol ratio were assessed. Dietary intake was estimated by a food frequency questionnaire. Results The subjects included in the highest tertile red meat (≥81.5 g/d) and saturated fatty acid from red meat consumption (≥4.3 g/d) had higher occurrence of central obesity (nearly 60%, p < 0.01), hypertriglyceridaemia (nearly 43%, p < 0.01) and metabolic syndrome (35%, p < 0.01). They also had higher values of homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein, and triglycerides:high-density lipoprotein cholesterol ratio, regardless of interfering factors. There were no associations of highest white meat tertile (≥39.4 g/d) and saturated fatty acid from white meat (≥1.0 g/d) consumption with the assessed parameters (p > 0.05). Conclusions Red meat consumption was cross-sectionally associated with the occurrence of central obesity, hypertriglyceridaemia, and metabolic syndrome as well as with higher homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein concentrations and triglycerides:high-density lipoprotein cholesterol ratio. The content of saturated fatty acid from red meat consumption may be a factor that contributed to this relationship, while white meat consumption was not associated with metabolic syndrome and the assessed biomarkers.

Obesity and diabetes: the link between adipose tissue dysfunction and glucose homeostasis.

Obesity and type 2 diabetes mellitus (T2DM) epidemics, which have already spread, imply the possibility of both conditions being closely related. Thus, the goal of the present review was to draw a parallel between obesity, adipose tissue (AT) changes, and T2DM development. To this end, a search was conducted in PubMed, MEDLINE and SciELO databases, using the following key words and their combinations: obesity; diabetes; insulin resistance; diet; weight loss; adipocin; inflammation markers; and interleukins. Based on a literature review, AT dysfunction observed in obesity is characterised by adipocyte hypertrophy, macrophage infiltration, impaired insulin signalling and insulin resistance. In addition, there is release of inflammatory adipokines and an excessive amount of NEFA promoting ectopic fat deposition and lipotoxicity in muscle, liver and pancreas. Recent evidence supports the hypothesis that the conception of AT as a passive energy storage organ should be replaced by a dynamic endocrine organ, which regulates metabolism through a complex adipocyte communication with the surrounding microenvironment. The present review demonstrates how glucose homeostasis is changed by AT dysfunction. A better understanding of this relationship enables performing nutritional intervention strategies with the goal of preventing T2DM.

Trypanosoma cruzi infection induces morphological reorganization of the myocardium parenchyma and stroma, and modifies the mechanical properties of atrial and ventricular cardiomyocytes in rats

BACKGROUND This study investigates morphofunctional adaptations of the heart stroma and parenchyma in rats that are chronically infected with Trypanosoma cruzi. METHODS Four-month-old male Wistar rats were randomized into control (n=14) and infected (n=14) groups. Infected animals were inoculated with T. cruzi Y strain. After 9 weeks, the animals were euthanized, and the right atrium (RA) and left ventricle (LV) were removed for biochemical, stereological, and cardiomyocyte mechanical analyses. RESULTS Infected animals presented cardiomyocyte atrophy and myocardial fibrosis. For these animals, the total volume, length, surface area, and cross-sectional area of cardiomyocytes were significantly reduced, and the total interstitial and collagen volumes were significantly increased in the RA and LV compared to the controls. The total volume and length of blood vessels were significantly increased in the LV, and the total blood vessel surface area was significantly higher in the RA of infected animals. RA and LV cardiomyocytes from infected animals exhibited a significant reduction in cell shortening (43.02% and 24.98%, respectively), prolongation of the time to the peak of contraction (17.09%) and the time to half relaxation (23.68%) compared to non-infected animals. Lipid hydroperoxides, but not mineral concentrations, were significantly increased in the RA and LV from infected animals, showing an inverse correlation with cell shortening. CONCLUSIONS T. cruzi infection induces global structural remodeling of the RA and LV in rats. This remodeling coexists with cardiomyocyte contractility dysfunction, which is possibly related to the abnormal organization of the myocardial stroma and increased cellular lipid peroxidation.