Decreased adiponectin/leptin ratio relates to insulin resistance in adults with obesity.

Adipose tissue dysfunction is a key mechanism that leads to adiposity-based chronic disease. This study aimed to investigate the reliability of the adiponectin/leptin ratio (AdipoQ/Lep) as an adipose tissue and metabolic function biomarker in adults with obesity, without diabetes. Data were collected from a clinical trial conducted in 28 adults with obesity (mean body mass index: 35.4 ± 3.7 kg/m2) (NCT02169778). With the use of a forward stepwise multiple linear regression model to explore the relationship between AdipoQ/Lep and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), it was observed that 48.6% of HOMA-IR variance was explained by triacylglycerols, AdipoQ/Lep, and waist-to-hip ratio (P < 0.001), AdipoQ/Lep being the strongest independent predictor (Beta = -0.449, P < 0.001). A lower AdipoQ/Lep was correlated with higher body mass index (Rs = -0.490, P < 0.001), body fat mass (Rs = -0.486, P < 0.001), waist-to-height ratio (Rs = -0.290, P = 0.037), and plasma resistin (Rs = -0.365, P = 0.009). These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance and emphasize that AdipoQ/Lep may be a promising early marker of insulin resistance development in adults with obesity.NEW & NOTEWORTHY Adiponectin/leptin ratio, triacylglycerols, and waist-to-hip ratio explained almost half of HOMA-IR variance in the context of obesity. This study provides evidence to support adipose tissue dysfunction as a central feature of the pathophysiology of obesity and insulin resistance. Early identification of individuals at higher risk of developing metabolic complications through adipose tissue dysfunction assessment and the staging of obesity and its transient phenotypes can contribute to improve therapeutic decision-making.

Physical exercise positively modulates nonalcoholic steatohepatitis-related hepatic endoplasmic reticulum stress.

Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic-based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER-related proapoptotic signaling, and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD [SS], voluntarily physically active animals with access to SCLD [SV], and endurance-trained animals with access to SCLD [ST] in the former and sedentary animals with access to liquid HFD [HS], voluntarily physically active animals with access to liquid HFD [HV], and endurance-trained animals with access to liquid HFD [HT] in the latter, respectively). Hepatic ER stress and ER-related proapoptotic signaling were evaluated by Western blot and reverse transcriptase-polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD-treated animals, VPA significantly decreased eukaryotic initiation factor-2 alpha (eIF2α). In HFD-treated animals, VPA significantly decreased eIF2α and phospho-inositol requiring enzyme-1 alpha (IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X-box binding protein 1 (sXBP1) and unspliced X-box binding protein 1; a significant increase of phosphorylated-eIF2α (p-eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p-eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH-related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α-X-box binding protein 1 pathway.

Effects of xenoestrogens in human M1 and M2 macrophage migration, cytokine release, and estrogen-related signaling pathways.

Bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and di(n-butyl)phthalate (DBP) are environmental estrogens that have been associated with a wide range of adverse health outcomes for which inflammation has also been hypothesized as a potentially involved mechanism and where macrophages play a central role. This study was carried out to evaluate if xenoestrogen (XE) treatment of classically (M1) or alternatively (M2) activated macrophages could affect their behavior. For this purpose, human peripheral blood monocyte-derived macrophages either unstimulated or activated with lipopolysaccharide (100 ng/mL, M1) or with interleukin (IL) 4 (15 ng/mL, M2) were treated with 17ß-estradiol (E2 ), BPA, DEHP and DBP alone or in combination with selective ERα or ERß antagonists. Migratory capability, cytokine release, and estrogen-associated signaling pathways were evaluated to assess macrophage function. All tested XEs had a tendency to stimulate M2 migration, an effect that followed the same direction than E2 . Moreover, all XEs significantly induced IL10 in M1 and decreased IL6 and globally decreased IL10, IL6, TNFα, and IL1ß release by M2 macrophages. However, DEHP and DBP significantly increased IL1ß release in M1 and M2 macrophages, respectively. Some of the effects described above were shown to be mediated by either ERα or ERß and were simultaneous to modulation of NF-κB, AP1, JNK, or ERK signaling pathways. We provide new evidence of the effect of XE on macrophage behavior and their mechanisms with relevance to the understanding of the action of environmental chemicals on the immune system and inflammation-associated diseases. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1496-1509, 2016.

Effects of environmental organochlorine pesticides on human breast cancer: putative involvement on invasive cell ability.

Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), and its metabolites p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyldichloroethane (p,p'-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p'-DDT, p,p'-DDE, and p,p'-DDD (50-1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals--depot differences and dysmetabolism implications.

BACKGROUND: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. OBJECTIVES: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. METHODS: AT samples (n=189) from obese patients (BMI ≥ 35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. RESULTS: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9 ± 204.2 compared to 155.1 ± 147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. CONCLUSION: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens.

Estrogen signaling in metabolic inflammation.

There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

Methotrexate enhances 3T3-L1 adipocytes hypertrophy.

Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and (3)H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 µM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. (3)H-Deoxyglucose ((3)H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and (3)H-thymidine incorporation (P < 0.05). MTX (0.1 µM) treatment increased lipid accumulation and basal (3)H-DG uptake by adipocytes (P < 0.05). In 0.1 µM MTX-treated adipocytes, insulin stimulation did not result in an increase of (3)H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX.

Characterization of an obese population: a retrospective longitudinal study from real-world data in northern Portugal.

BACKGROUND: Obesity is a serious and largely preventable global health problem. Obesity-related electronic health records can be a useful resource to identify and address obesity. The analysis of real-world data from T82-coded (International Classification of Primary Care coding, for obesity) primary care individuals can be an excellent national source of data on obesity's prevalence, characteristics, and impact on the National Health Service. METHODS: Retrospective longitudinal study, based on a database of electronic medical records, from the Regional Health Administration of northern Portugal. The study objectives were to determine the prevalence of obesity and to characterize an adult obese population in northern Portugal from a bio-demographic point of view along with profiles of comorbidities and the use of health resources. This study used a database of 266,872 patients in December 2019 and screened for diagnostic code T82 from the International Classification of Primary Care. RESULTS: The prevalence of obesity was 10.2% and the highest prevalence of obesity was in the 65-74 age group (16.1%). The most prevalent morbidities in patients with obesity as coded through ICPC-2 were K86 (uncomplicated hypertension), T90 (non-insulin-dependent diabetes), and K87 (complicated hypertension). Descriptive information showed that T82 subjects used more consultations, medications, and diagnostic tests than non-T82 subjects. CONCLUSIONS: Routine recording of weight and height deserves special attention to allow obesity recognition at an early stage and move on to the appropriate intervention. Future work is necessary to automate the codification of obesity for subjects under 18 years of age, to raise awareness and anticipate the prevention of problems associated with obesity. Practical strategies need to be implemented, such as the creation of a specific program consultation with truly targeted approaches to obesity.

Measuring adherence to inhaled control medication in patients with asthma: Comparison among an asthma app, patient self-report and physician assessment.

BACKGROUND: Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. METHODS: This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0-100). RESULTS: A total of 193 patients (72% female; median [P25-P75] age 28 [19-41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0-71]%; 1 month: 18 [0-48]%) than patient self-report (80 [60-95]) and physician assessment (82 [51-94]) (p < 0.001). A negligible non-significant correlation was found between the app and subjective measurements (ρ 0.118-0.156, p > 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). CONCLUSIONS: Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.

Symptoms of anxiety and depression in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

OBJECTIVES: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms. METHODS: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built. RESULTS: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression. CONCLUSION: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer-promoting secretory profile.

BACKGROUND/AIMS: The microenvironment produces important factors that are crucial to prostate cancer (PCa) progression. However, the extent to which the cancer cells stimulate periprostatic adipose tissue (PPAT) to produce these proteins is largely unknown. Our purpose was to determine whether PCa cell-derived factors influence PPAT metabolic activity. METHODS: Primary cultures of human PPAT samples from PCa patients (adipose tissue organotypic explants and primary stromal vascular fraction, SVF) were stimulated with conditioned medium (CM) collected from prostate carcinoma (PC3) cells. Cultures without CM were used as control. We used multiplex analysis and ELISA for protein quantification, qPCR to determine mitochondrial DNA (mtDNA) copy number and zymography for matrix metalloproteinase activity, in order to evaluate the response of adipose tissue explants and SVFs to PC3 CM. RESULTS: Stimulation of PPAT explants with PCa PC3 CM induced adipokines associated with cancer progression (osteopontin, tumoral necrosis factor alpha and interleukin-6) and reduced the expression of the protective adipokine adiponectin. Notably, osteopontin protein expression was 13-fold upregulated. Matrix metalloproteinase 9 activity and mitochondrial DNA copy number were higher after stimulation with cancer CM. Stromovascular cells from PPAT in culture were not influenced by tumor-derived factors. CONCLUSION: The modulation of adipokine expression by tumor CM indicates the pervasive extent to which tumor cells command PPAT to produce factors favorable to their aggressiveness.

Optimization and validation of organochlorine compounds in adipose tissue by SPE-gas chromatography.

Scientific evidence has shown an association between organochlorine compounds (OCC) exposure and human health hazards. Concerning this, OCC detection in human adipose samples has to be considered a public health priority. This study evaluated the efficacy of various solid-phase extraction (SPE) and cleanup methods for OCC determination in human adipose tissue. Octadecylsilyl endcapped (C18-E), benzenesulfonic acid modified silica cation exchanger (SA), poly(styrene-divinylbenzene (EN) and EN/RP18 SPE sorbents were evaluated. The relative sample cleanup provided by these SPE columns was evaluated using gas chromatography with electron capture detection (GC-ECD). The C18-E columns with strong homogenization were found to provide the most effective cleanup, removing the greatest amount of interfering substance, and simultaneously ensuring good analyte recoveries higher than 70%. Recoveries > 70% with standard deviations (SD) < 15% were obtained for all compounds under the selected conditions. Method detection limits were in the 0.003-0.009 mg/kg range. The positive samples were confirmed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The highest percentage found of the OCC in real samples corresponded to HCB, o,p'-DDT and methoxychlor, which were detected in 80 and 95% of samples analyzed respectively.

Tailoring gut microbiota with a combination of Vitamin K and probiotics as a possible adjuvant in the treatment of rheumatic arthritis: a systematic review.

Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease.

Intermittent energy restriction ameliorates adipose tissue-associated inflammation in adults with obesity: A randomised controlled trial.

BACKGROUND & AIMS: Although intermittent energy restriction (IER) seems to be as effective as continuous energy restriction (CER) for weight loss, there is still a need to determine the putative effect of this strategy upon the metabolic-inflammatory status. This study aimed to compare the effects of IER versus CER on cardiometabolic and inflammatory markers, over a 12-week period, in adults with obesity. METHODS: Twenty-eight Norwegian adults (20-55 years) with obesity [body mass index: 35.4 (3.7) kg/m2] from a clinical trial (NCT02169778) who completed a 12-weeks diet-induced weight loss as IER (n = 14) or CER (n = 14) were included in this study. Cardiometabolic, adipokines and inflammatory markers were evaluated at baseline and after the intervention. Plasma levels of 13 inflammatory cytokines and chemokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-33) and 4 adipokines (adiponectin, adipsin, leptin and resistin) were measured through multiplex bead-based flow cytometric immunoassays. RESULTS: Both interventions resulted in comparable reductions in fasting glucose and insulin concentrations, lipid profile biomarkers, and adipokines. There were significant differences in HOMA-IR between interventions, with a more pronounced reduction in the IER group (-3.7 vs -1.6, P = 0.040). Inflammatory cytokines and chemokines decreased significantly in the IER group only. Differences in the relative changes of IL-1ß (-48.5 vs 58.2%, P = 0.011), IFN-γ (-53.2 vs 45.1%, P = 0.023), MCP-1 (-22.0 vs 17.4%, P = 0.023), IL-18 (-40.8 vs 10.1%, P = 0.019), IL-23 (-64.8 vs 44.0%, P = 0.011) and IL-33 (-53.4 vs 35.7%, P = 0.028) were statistically significant between groups, with improvements in the inflammatory profile in the IER group. CONCLUSIONS: Our results suggest that a 12-weeks intermittent energy restriction, in comparison to a continuous energy strategy, could be advantageous to reduce inflammation associated with obesity, and consequently improve insulin resistance, regardless of the amount of weight loss. Registered under ClinicalTrials.gov Identifier no. NCT02169778.

Gut Microbiota, in the Halfway between Nutrition and Lung Function.

The gut microbiota is often mentioned as a "forgotten organ" or "metabolic organ", given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a "good" microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut-lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases.

Effect of polyphenols on the intestinal and placental transport of some bioactive compounds.

Polyphenols are a group of widely distributed phytochemicals present in most foods of vegetable origin. A growing number of biological effects have been attributed to these molecules in the past few years and only recently has their interference with the transport capacity of epithelial barriers received attention. This review will present data obtained concerning the effect of polyphenols upon the transport of some compounds (organic cations, glucose and the vitamins thiamin and folic acid) at the intestinal and placental barriers. Important conclusions can be drawn: (i) different classes of polyphenols affect transport of these bioactive compounds at the intestinal epithelia and the placenta; (ii) different compounds belonging to the same phenolic family often possess opposite effects upon transport of a given molecule; (iii) the acute and chronic/short-term and long-term exposures to polyphenols do not produce parallel results and, therefore, care should be taken when extrapolating results; (iv) the effect of polyphenolics in combination may be very different from the expected ones taking into account the effect of each of these compounds alone, and so care should be taken when speculating on the effect of a drink based on the effect of one component only; (v) care should be taken in drawing conclusions for alcoholic beverages from results obtained with ethanol alone. Although most of the data reviewed in the present paper refer to in vitro experiments with cell-culture systems, these studies raise a concern about possible changes in the bioavailability of substrates upon concomitant ingestion of polyphenols.

Chronic inflammation in obesity and the metabolic syndrome.

The increasing incidence of obesity and the metabolic syndrome is disturbing. The activation of inflammatory pathways, used normally as host defence, reminds the seriousness of this condition. There is probably more than one cause for activation of inflammation. Apparently, metabolic overload evokes stress reactions, such as oxidative, inflammatory, organelle and cell hypertrophy, generating vicious cycles. Adipocyte hypertrophy, through physical reasons, facilitates cell rupture, what will evoke an inflammatory reaction. Inability of adipose tissue development to engulf incoming fat leads to deposition in other organs, mainly in the liver, with consequences on insulin resistance. The oxidative stress which accompanies feeding, particularly when there is excessive ingestion of fat and/or other macronutrients without concomitant ingestion of antioxidant-rich foods/beverages, may contribute to inflammation attributed to obesity. Moreover, data on the interaction of microbiota with food and obesity brought new hypothesis for the obesity/fat diet relationship with inflammation. Beyond these, other phenomena, for instance psychological and/or circadian rhythm disturbances, may likewise contribute to oxidative/inflammatory status. The difficulty in the management of obesity/metabolic syndrome is linked to their multifactorial nature where environmental, genetic and psychosocial factors interact through complex networks.

Metabolically Healthy Obesity-Heterogeneity in Definitions and Unconventional Factors.

The concept of heterogeneity among obese individuals in their risk for developing metabolic dysfunction and associated complications has been recognized for decades. At the origin of the heterogeneity idea is the acknowledgement that individuals with central obesity are more prone to developing type 2 diabetes and cardiovascular disease than those with peripheral obesity. There have been attempts to categorize subjects according to their metabolic health and degree of obesity giving rise to different obese and non-obese phenotypes that include metabolically unhealthy normal-weight (MUHNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Individuals belonging to the MHO phenotype are obese according to their body mass index although exhibiting fewer or none metabolic anomalies such as type 2 diabetes, dyslipidemia, hypertension, and/or unfavorable inflammatory and fribinolytic profiles. However, some authors claim that MHO is only transient in nature. Additionally, the phenotype categorization is controversial as it lacks standardized definitions possibly blurring the distinction between obesity phenotypes and confounding the associations with health outcomes. To add to the discussion, the factors underlying the origin or protection from metabolic deterioration and cardiometabolic risk for these subclasses are being intensely investigated and several hypotheses have been put forward. In the present review, we compare the different definitions of obesity phenotypes and present several possible factors underlying them (adipose tissue distribution and cellularity, contaminant accumulation on the adipose tissue, dysbiosis and metabolic endotoxemia imposing on to the endocannabinoid tone and inflammasome, and nutrient intake and dietary patterns) having inflammatory activation at the center.

A simple remote nutritional screening tool and practical guidance for nutritional care in primary practice during the COVID-19 pandemic.

Challenging periods like the COVID-19 pandemic require fast and efficient adaptations of the healthcare system. It is vital that every patient has access to nutritional care as a part of primary healthcare services, even if social distancing measures are adopted. Therefore, we propose a simple remote nutritional screening tool and practical guidance for nutritional care in primary practice, and their implementation into telemedicine processes and digital platforms suitable for healthcare providers. The acronym for the tool is R-MAPP, as for Remote - Malnutrition APP, while the tool will be available also as an app. This protocol consists of two simple validated clinical tools for identifying nutritional risk and loss of muscle mass and function -Malnutrition Universal Screening Tool ('MUST') and SARC-F (5-item questionnaire: Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls) - and additional practical guidance on nutritional interventions for family physicians.