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Despite the known effects of diet on gut microbiota composition, not many studies have evaluated the relationship between distinct dietary patterns and gut microbiota. The aim of our study was to determine whether gut microbiota composition could be a useful indicator of a long-term dietary pattern. We collected data from 89 subjects adhering to omnivorous, vegetarian, vegan, and low-carbohydrate, high-fat diet that were equally distributed between groups and homogenous by age, gender, and BMI. Gut microbiota composition was analyzed with a metabarcoding approach using V4 hypervariable region of the 16S rRNA gene. K-means clustering of gut microbiota at the genus level was performed and the nearest neighbor classifier was applied to predict microbiota clustering classes. Our results suggest that gut microbiota composition at the genus level is not a useful indicator of a subject’s dietary pattern, with the exception of a vegan diet that is represented by a high abundance of Prevotella 9. Based on our model, a combination of 26 variables (anthropometric measurements, serum biomarkers, lifestyle factors, gastrointestinal symptoms, psychological factors, specific nutrients intake) is more important to predict an individual’s microbiota composition cluster, with 91% accuracy, than the dietary intake alone. Our findings could serve to develop strategies to educate individuals about changes of some modifiable lifestyle factors, aiming to classify them into clusters with favorable health markers, independent of their dietary pattern.

Regular consumption of Helichrysum italicum infusion improves body composition, while Helichrysum arenarium ameliorates lipid profile. Therefore, both hold great potential for the management of metabolic syndrome.

L-leucyl-leucine methyl ester (LLOMe) is a lysosomotropic detergent, which was evaluated in clinical trials in graft-vs-host disease because it very efficiently killed monocytic cell lines. It was also shown to efficiently trigger apoptosis in cancer cells, suggesting that the drug might have potential in anticancer therapy. Using U-937 and THP-1 promonocytes as models for monocytic cells, U-87-MG and HeLa cells as models for cancer cells, and noncancerous HEK293 cells, we show that the drug triggers rapid cathepsin C-dependent lysosomal membrane permeabilization, followed by the release of other cysteine cathepsins into the cytosol and subsequent apoptosis. However, monocytes were found to be far more sensitive to the drug than the cancer and noncancer cells, which is most likely a consequence of the much higher intracellular levels of cathepsin C-the most upstream molecule in the pathway-in monocytic cell lines as compared to cancer cells. Overexpression of cathepsin C in HEK293 cells substantially enhances their sensitivity to the drug, consistent with the crucial role of cathepsin C. Major involvement of cysteine cathepsins B, S, and L in the downstream signaling pathway to mitochondrial cell death was confirmed in two gene ablation models, including the ablation of the major cytosolic inhibitor of cysteine cathepsins, stefin B, in primary mouse cancer cells, and simultaneous ablation of two major cathepsins, B and L, in mouse embryonic fibroblasts (MEFs). Deletion of stefin B resulted in sensitizing primary murine breast cancer cells to cell death without affecting the release of cathepsins, whereas simultaneous ablation of cathepsins B and L largely protected MEFs against cell death. However, due to the extreme sensitivity of monocytes to LLOMe, it appears that the drug may not be suitable for anticancer therapy due to risk of systemic toxicity.

Objective: Understanding the impact of stress on emotional and external eating behaviors and the psychological and the associated metabolic factors can help in designing subsequent interventions to protect health. In particular, psychological trait-like construct related to eating has been shown to be an important target for intervention. Methods and measures: This study aimed to investigate the biochemical variables associated with a decrease in emotional and external eating behaviors due to 12-week ketogenic diet (12KD) in 35 adult participants (12 males) with obesity. Results: Absolute changes in emotional and external eating were independent of changes in body mass, nutritional intake, and Δ cortisol, but were predicted with increases in serum β-hydroxybutyrate (BHB) and decreases in serum peripheral neuropeptide Y (pNPY) (all p’s

This study was focused on the creation of high-protein bars formulated using whey protein isolate (24%) and soy protein isolate (6%) as the sources of proteins, oat flakes and inulin, both abundant in dietary fibres, and creatine monohydrate and other minor ingredients (vitamin and mineral mixture, potassium sorbate) to achieve the requirements for a meal replacement formula for physically active people. The nutritional profile of the high-protein bar was examined (energy 1215 kJ/288 kcal, protein 34.1 ± 0.20 g, fat 6.01 ± 0.13 g of which was saturated 3.12 ± 0.08 g, fibre 3.10 ± 0.17 g carbohydrate 23.0 ± 0.16 g of which sugars 1.50 ± 0.19 g and starch 21.5 ± 0.11 g in 100 g), and sensory properties with instrumental parameters (texture and colour) were determined and compared with bars commercially available on the market. The created high-protein bar was sensorily acceptable in comparison to other commercially available bars. The dietary intervention study was conducted on elite athletes (professional handball players) to evaluate effects of created versus control bar consumption on their metabolic parameters. The baseline characteristics (mean age, body mass index (BMI), fat mass, muscle mass, lean mass and fat percentage) of the athletes (8) were determined at the start of the study. The cross-over intervention study was organized in two successive phases (5 days each) with a seven-day long washout period between phases. Bars were consumed after the afternoon training unit. Blood samples were collected at the start and the end of the intervention study to analyse the metabolic profiles of the athletes. Serum levels of high-density cholesterol (HDL), low-density cholesterol (LDL) and total cholesterol (HOL), glucose, triacylglycerides (TAG), total and direct bilirubin, creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. The results showed that bar consumption significantly decreased serum aspartate transaminase (AST) and lactate dehydrogenase (LDH) and increased total and direct bilirubin levels, suggesting lower exercise-induced muscle damage and increased antioxidative response, respectively. Therefore, it can be concluded that the consumption of the created high-protein bar was able to improve physiological adaptation after training.

Obesity is a chronic condition involving low-grade inflammation and increased oxidative stress; thus, obese and overweight people have lower values of serum bilirubin. Essentially, bilirubin is a potent endogenous antioxidant molecule with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties. This review paper presents the interplay between obesity-related pathological processes and bilirubin, with a focus on adipose tissue and adipokines. We discuss potential strategies to mildly increase serum bilirubin levels in obese patients as an adjunctive therapeutic approach.

Helichrysum italicumis an aromatic plant with promising pharmacological activities. Bioactive compounds found in plants represent an important alternative treatment for weight loss and an infusion ofH. italicumcontains compounds which could have such effect. Our aim was, therefore, to investigate its acute effects on resting energy expenditure (REE) and possible differences in substrate oxidation in a pilot study. A dried, ground plant material ofH. italicumssp.italicumwas infused with hot water and chemically characterized with HPLC-MS analysis. Sensory evaluation of herbal tea was performed. A randomized, crossover, controlled pilot study was then conducted on eleven healthy male subjects. The REE and substrate oxidation were measured by indirect calorimetry at baseline and 30 and 120 min after ingestion of infusion or hot water. The expression of genes involved in lipid metabolism was examined inH. italicuminfusion-treated hepatocytes. Several phenolic classes were identified in the infusion, caffeoylquinic acids were the most abundant, followed by pyrones and flavonols. A single ingestion ofH. italicuminfusion significantly increased REE by 4% and fat oxidation by 12% compared to hot water ingestion. A significant 2-fold up-regulation of β-oxidation-related genes in HepG2 cells, exposed toH. italicuminfusion, was detected. This pilot study suggests thatH. italicuminfusion possesses bioactive substances with potential application in obesity prevention, which could, with additional studies, become an economically interesting novel application of the plant. Clinical trial registration number: NCT04818905

Background: Many risk factors lead to opioid use and drug-related problems. One of the challenges to understand behavioural factors, drug problems and psychopathology is to identify biological markers that are suitable for research on broad substance abuse and dependence involving human participants. Aims: The study has examined the relationships between the self-reported childhood history of trauma, parental bonding, psychopathology, impulsivity, current resiliency, two neuropeptides, possible markers of behaviour and emotion regulation, and severity of drug-related problems. Methods: One hundred and sixty-seven individuals with a history of opioid use completed questionnaires. Serum neuropeptide Y (NPY) and substance P (SP) levels were analysed. Moderating and mediating relationships between variables were examined using structural equation modelling (SEM). Results: Antisocial features, depression, impulsivity, SP, NPY, emotional neglect and resilience are associated with severity of drug- related problems. SP is associated with antisocial personality traits. Conclusions: The novelty of this study is the proposed possible link between biochemical markers, antisocial features and behavioural and emotional regulation. Serum NPY and SP levels have a potential to be used as a biomarker in opioid users before and in the treatment process to account for interactions between biological vulnerabilities and childhood risk factors in predicting behavioural adjustment and more severe drug-related problems.

The ketogenic diet (KD) is being increasingly promoted as a strategy to fight obesity. Although the KD is effective for weight loss and weight control, comprehensive determination of its relationship with biochemical, physiological and psychological changes is still largely unexplored. We hypothesized that a 12-week KD (12KD) would significantly affect body weight, physical performance, cognitive function, eating behaviors, the metabolic and hormonal profile in obese adults, although differently in men and women. In an uncontrolled intervention, 35 sedentary obese adults (13 men, 25 women), aged 37 ± 7 years with a BMI 36.1 ± 5.6 kg/m2 underwent a 12KD between March 2017 and June 2017 at the University of Primorska. The 12KD resulted in decreased appetite, significant weight loss of participants (−18 ± 9 kg men vs. -11 ± 3 kg women; P

Due to limited data about the impact of lockdown on health status, the present study aimed to investigate the impact of COVID-19-related lockdown on changes in dietary habits, physical activity and serum markers in healthy adults. A total of 38 asymptomatic adults aged from 23 to 59 with a normal BMI (22.5 kg/m2) participated in baseline and post-lockdown measurements that included dietary and physical activity assessment, anthropometric measurements and blood samples, and the lockdown survey which included dietary assessment and questionnaires about changes in lifestyle and physical activity. A decreased diet quality during lockdown was observed (Healthy Eating Index reduced from 64.59 to 61.08), which returned to near baseline post-lockdown. Energy intake decreased during lockdown (p = 0.002) and returned to baseline post-lockdown. Despite lower physical activity levels during lockdown (p = 0.035), we observed no significant changes in body composition. However, we observed a significant increase in serum glucose (p = 0.005), total cholesterol (p = 0.003), and low-density lipoprotein (LDL) (p = 0.049) post-lockdown. Increase in serum glucose levels was pronounced in subjects with higher increase in energy intake (p = 0.039), increased omega-6 fatty acids intake (p = 0.016), those who were exposed to several risky contacts (p = 0.018, compared to those with less risky contacts) and those who were not active in nature (p = 0.008, compared to those active in nature). Increased serum LDL was correlated to decreased monounsaturated fatty acids intake (p = 0.028). Within the limits of this preliminary report, changes in serum markers observed among healthy subjects point to a possible impact of COVID-19-related lockdown on adults’ health to be confirmed in larger groups.

This article belongs to the Section Nutrition and Metabolism., The dynamics and diversity of human gut microbiota that can remarkably influence the wellbeing and health of the host are constantly changing through the host’s lifetime in response to various factors. The aim of the present study was to determine a set of parameters that could have a major impact on classifying subjects into a single cluster regarding gut bacteria composition. Therefore, a set of demographical, environmental, and clinical data of healthy adults aged 25–50 years (117 female and 83 men) was collected. Fecal microbiota composition was characterized using Illumina MiSeq 16S rRNA gene amplicon sequencing. Hierarchical clustering was performed to analyze the microbiota data set, and a supervised machine learning model (SVM; Support Vector Machines) was applied for classification. Seventy variables from collected data were included in machine learning analysis. The agglomerative clustering algorithm suggested the presence of four distinct community types of most abundant bacterial phyla. Each cluster harbored a statistically significant different proportion of bacterial phyla. Regarding prediction, the most important features classifying subjects into clusters were measures of obesity (waist to hip ratio, BMI, and visceral fat index), total body water, blood pressure, energy intake, total fat, olive oil intake, total fiber intake, and water intake. In conclusion, the SVM model was shown as a valuable tool to classify healthy individuals based on their gut microbiota composition., The study was supported by the European foundation for alcohol research through a Spanish Slovenian bilateral project (ERAB EA. 14.44). This work was also supported by the Slovenian Research Agency (Programme P1-0386).

Chili and its main active ingredient capsaicin have been shown to induce several favorable biological activities. In the present study we have tested the effect of three chili sauces mimicking popular commercially available chili sauces with an increasing amount of capsaicinoids on a broad range of serum biochemical markers in thirty healthy subjects. We show that in the region where daily use of chili is traditionally low, moderate consumption of 4.4 mg of capsaicinoids per day has beneficial health effects, such as decrease in glucose level, LDL cholesterol and C-reactive protein. However, when a product with higher daily dose of capsaicinoids (16.7 mg/day) was consumed, those effects were lost. Considering that biochemical marker levels returned to the initial levels after a week-long wash-out period, we suggest that regular intake of moderate amounts of chili product would be most profitable.

peer-reviewed, Buckwheat (BW) has attracted increasing attention as an important functional food because of its beneficial effects on health. Therefore, three different instant porridges were developed: BW – enriched highprotein (A), corn-based high-protein (B) and corn-based non-protein (C), and their effects on selected clinical markers were investigated. A randomised, cross-over intervention study was performed among 34 participants with mild to moderate hypercholesterolemia. Intake of porridge A significantly reduced serum levels of total cholesterol, LDL cholesterol, triacylglycerol and, uric acid and, significantly increased serum adiponectin levels, HDL cholesterol, and fat-free mass. In conclusion, the intake of porridge A as a functional food may improve lipid profile and may reduce inflammation. These findings may support the view that consuming BW as an element in porridge is an effective and convenient nutritional therapy for improving metabolic parameters in participants with metabolic syndrome components., The authors would like to thank all the subjects for volunteering in this study and nurses of the Faculty of Health Sciences for taking the blood samples, and to prof. Philip Burt for proof reading the article. The authors would also like to thank Vanja Pahor and the Izola General Hospital biochemical laboratory staff and Slavica Karanović from EuroTim, Novi Sad, who helped to formulate and produce the porridges. This work was supported by the Slovenian Research Agency (research core funding No. P1- 0386; the bilateral project “Evaluation of functional cereal-based products for people with metabolic disorders”, No. BI-RS/14-15-048) and the Ministry of Education, Science and Technological Development, Republic of Serbia (Project No: TR-31029).

Obesity and overweight are major contributors to the burden of chronic disease. Both are defined as abnormal or excessive fat accumulation and by increased production of free radicals leading to oxidative stress. The aim of the present study was to evaluate whether overweight and fat accumulation is associated with serum total antioxidant capacity (TAC) in men and women, irrespective of nutritional habits, nutrient intakes, physical activity, smoking, and other confounders, which may be responsible for modifying the association between serum TAC and overweight/obesity measures. This cross-sectional study was conducted on 60 normal weight and 60 overweight adults aged 25–49. All participants underwent standard anthromorphological measurements of body composition, blood pressure and biochemical measurements, aerobic capabilities assessment and dietary intake evaluation. TAC was measured by using the photochemioluminescence method. All data were analysed with SPSS software. Men had higher values of TAC than women and concentrations of TAC were significantly higher in overweight subjects compared to normal weight subjects. In the present study TAC tended to be increased by various metabolic risk factors, especially overweight/obesity parameters (body mass index, body fat), inflammation and increased serum levels of Cysteine, irrespective of nutritional habits, nutrient intakes, physical activity and smoking. Overweight and obesity at an early stage may stimulate TAC. Therefore, the elevation of TAC in overweight adults may be a compensatory response to oxidative stress, generated by reactive oxygen species.

Increased intestinal permeability has been shown to be involved in several diseases associated with low-grade chronic inflammation, including obesity and metabolic syndrome. In the last decade, growing evidence shows the beneficial effects of probiotic-containing food supplementation on these conditions. In this crossover intervention study on 28 asymptomatic overweight adults, we tested the effects of a 3-wk kefir supplementation compared with a 3-wk milk supplementation on serum zonulin levels. The effects on serum glucose, triacylglycerols, low-density lipoproteins, high-density lipoproteins, total cholesterol, markers of inflammation (C-reactive protein and adiponectin), anthropometric variables, mood, and appetite were also determined. Kefir supplementation resulted in a greater improvement of serum zonulin levels (F = 6.812, η2 = 0.275), whereas a significant yet similar improvement in lipid profile and serum glucose levels was found in both supplementations. Positive mood was slightly but significantly enhanced with kefir supplementation, and reduced with milk supplementation. The C-reactive protein, adiponectin, and appetite were unaffected. In conclusion, supplementation with both dairy products had health beneficial effects, but only kefir showed an effect on the intestinal barrier dysfunction marker.

A 12-wk ketogenic diet was found to have many beneficial effects in healthy obese adults, but it is not clear if the supply of micronutrients is adequate.In 35 adult individuals with body mass index30, the intakes of minerals and their serum levels were analyzed at baseline and at weeks 4 and 12 of the ketogenic diet intervention. The intake of vitamins and serum antioxidative potential were also investigated.Throughout the diet the intakes of magnesium, calcium, iron, phosphorus, and potassium were less than recommended values, but serum levels always remained within the reference range. Nevertheless, the level of calcium decreased significantly (from 2.52 ± 0.10 mmol/L at baseline to 2.36 ± 0.07 mmol/L at week 12, P0.001), which could be due to the omission of legumes and reduced dairy intake or because of the high fat intake alone. The levels of phosphate increased concomitantly. Calcium serum levels were negatively associated with ω-6 but not with ω-3 unsaturated fatty acid intake. The intakes of water-soluble vitamins were also too low. However, the antioxidative potential of serum did not change during intervention.Careful choice of foods that will provide the necessary micronutrients is of utmost importance when consuming ketogenic diet. In the 12 wk study the decreased intakes were not reflected in serum values, but special attention to calcium should be advised if such diet is recommended for longer periods.

Objectives. Obesity and overweight are chronic disorders of multifactorial origin that are characterized by high oxidative status and by chronic activation of macrophages in peripheral tissues. Effective therapeutic approaches to lower inflammation and oxidative stress are currently of general interest. Royal jelly (RJ) is a functional food with a broad range of pharmacological activities, mainly used by healthy individuals or borderline patients to protect themselves against disease onset. The objective of this randomized, double-blind, placebo-controlled trial was to investigate the effects of RJ supplementation on metabolic profile and oxidative and inflammatory parameters in asymptomatic overweight adults, considered at an early stage of developing metabolic syndrome. Material and Methods. The experimental group (n=30) was given RJ and the control group (n=30) was provided with a placebo for eight weeks. Anthropometric, biochemical parameters, biomarkers of oxidative stress, and inflammation were assessed at baseline, after 4 and 8 weeks of the intervention, and after additional 2 weeks of follow up. Results and Conclusion. Compared with the placebo, RJ supplementation demonstrated a statistically significant decrease in total cholesterol (6.7%; p=0.041) and inflammatory marker C-reactive protein (19%; p=0.027), whereas significant increases were observed in anti-inflammatory marker adiponectin (34%; p=0.011), endogenous antioxidants bilirubin (35%; p=0.002) and uric acid (5%; p=0.018), total antioxidant capacity in serum (54%; p=0.005), and leptin (17%; p=0.025). The present study demonstrated positive effects of RJ administration on lipid profile, satiety, inflammation, and antioxidant capacity in overweight adults. Therefore, our study supports the benefits of RJ supplementation for the improvement of human health.

Background: This study has examined the relationships and interactions between serum brain-derived neurotrophic factor (BDNF) levels, BDNF Val66Met polymorphism and self-reported risk-taking behaviour in individuals with a history of heroin use undergoing outpatient treatment in comparison to healthy individuals. Methods: We enrolled 167 heroin users and 86 healthy subjects and examined serum BDNF levels, Val66Met polymorphism, and personal characteristics using Connor Davidson Resilience Scale, Risk-taking (RT) propensity questionnaire, and Personality Assessment Inventory. Results: Heroin users had significantly higher serum BDNF levels than controls. In addition, serum BDNF levels were significantly higher in Val/Val carriers than in Met/Val or Met/Met in all recruited subjects. Furthermore, a stepwise multiple regression analysis of serum BDNF levels as a dependent variable with related factors showed that in heroin users, Alcohol Use Disorder Identification Test score, anxiety and RT score were found as independent contributors to serum BDNF levels. When performing gene-environment interaction it was additionally found that heroin users with self-reported high risk-taking behaviour had significantly lower levels of serum BDNF among heroin users with the Met allele. Conclusions: These results indicate that genetic variant Met66 decreased the serum BDNF levels in combination with self-reported risk-taking propensity among heroin users. If results of future work confirm the influence of this combined effect between neurotrophic genotype and risk-taking behaviour, 66Met carriers might require higher levels of intervention to overcome their drug use pattern and risky behaviour.

Low-grade systemic inflammation due to obesity is considered to be the key link between obesity and obesity-related disorders. The hypothesis was tested that significant alterations in inflammatory markers and adipokines would occur over a multidisciplinary intervention and that these changes might also be important for improvement of cardiovascular risk factors.Thirty-tree overweight adults completed a 6-month multidisciplinary intervention program to evaluate the effects of a personalized dietary program based on the individual's resting metabolic rate (RMR) on anthropometric parameters, aerobic and anaerobic capabilities, metabolic profile, inflammation, and body image satisfaction. Body composition, physical activity, anaerobic capabilities, RMR, metabolic profile, and low-grade inflammation were measured. Diet composition and body image dissatisfaction were also assessed.After 6 months of multidisciplinary intervention the participants showed significantly decreased body weight, waist circumference (WC), and the inflammatory markers tumor necrosis factor-α, C-reactive protein, and visfatin. They also showed increased anti-inflammatory adiponectin and consequently decreased serum insulin, HOMA-IR, and total cholesterol. The important findings of the study were that reduction of sugars and saturated fatty acids in the diet, coupled with an increase in exercise, significantly correlated with reduction of WC and body mass index. In addition, positive correlations between ∆ BMI, ∆ WC, ∆ trunk fat, inflammation, and cardiovascular risk factors were demonstrated.Weight loss in combination with increased physical activity, a negative energy balance, and diet adjustment was associated with lower inflammation and consequently with lower cardiovascular risk factors.

Objective Low levels of bilirubin have recently been associated with obesity, diabetes mellitus, and metabolic syndrome. Here, we hypothesized that serum bilirubin levels might be already altered in overweight asymptomatic middle-aged individuals before full development of the metabolic syndrome. Methods Healthy nonsmoking adults aged 25–49 (64 women and 32 men) participated in this cross-sectional study. All participants who reported stable weight within the last three months underwent standard anthropomorphological measurements of body composition, blood pressure measurements, aerobic and anaerobic capabilities assessment, dietary intake evaluation, and fasting serological measurements of total and direct bilirubin, glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein. Participants were divided into normal-weight and overweight groups. Linear correlation and multiple regression analyses were used to examine the association of serum bilirubin levels with all metabolic syndrome risk factor changes. Results Serum bilirubin levels were lower in overweight healthy individuals of both sexes, and were negatively associated with abdominal obesity, insulin resistance, fasting glucose, fasting insulin, fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein levels but positively associated with aerobic body capabilities. Conclusion Our findings suggest that serum bilirubin levels have the potential to be employed as an early biomarker for indicating asymptomatic individuals at increased risk of developing metabolic syndrome.

As a model for defining the role of lysosomal cathepsins in apoptosis, we characterized the action of the lysosomotropic agent LeuLeuOMe using distinct cellular models. LeuLeuOMe induces lysosomal membrane permeabilization, resulting in release of lysosomal cathepsins that cleave the proapoptotic Bcl-2 family member Bid and degrade the antiapoptotic member Bcl-2, Bcl-xL, or Mcl-1. The papain-like cysteine protease inhibitor E-64d largely prevented apoptosis, Bid cleavage, and Bcl-2/Bcl-xL/Mcl-1 degradation. The pancaspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)fluoromethyl ketone failed to prevent Bid cleavage and degradation of anti-apoptotic Bcl-2 homologues but substantially decreased cell death, suggesting that cathepsin-mediated apoptosis in these cellular models mostly follows a caspase-dependent pathway. Moreover, in vitro experiments showed that one or more of the cysteine cathepsins B, L, S, K, and H could cleave Bcl-2, Bcl-xL, Mcl-1, Bak, and BimEL, whereas no Bax cleavage was observed. On the basis of inhibitor studies, we demonstrate that lysosomal disruption triggered by LeuLeuOMe occurs before mitochondrial damage. We propose that degradation of anti-apoptotic Bcl-2 family members by lysosomal cathepsins synergizes with cathepsin-mediated activation of Bid to trigger a mitochondrial pathway to apoptosis. Moreover, XIAP (X-chromosome-linked inhibitor of apoptosis) was also found to be a target of cysteine cathepsins, suggesting that cathepsins can mediate caspase-dependent apoptosis also downstream of mitochondria.

The potential role of cysteine cathepsins, especially cathepsin B, in Fas/CD95-induced apoptosis was investigated using wild-type and cathepsin B-deficient primary skin fibroblasts. Apoptosis was induced with an anti-Fas/CD95 antibody in the presence of cycloheximide and no difference was observed between the two genotypes. First cells with damaged mitochondria were observed approximately 3h post apoptosis induction and their number was significantly increased after 11h. In contrast, cells with damaged lysosomes were only seen after 15h with no difference between the two genotypes. Moreover, Bid cleavage was found to be diminished in cathepsin B-deficient cells. These results suggest that cysteine cathepsins have no active role in Fas/CD95 apoptosis.

Coffee consumption is negatively associated with risk of type 2 diabetes and cardiovascular mortality. Coffee roasting can greatly modify the quality-quantitative characteristics of bioactive compounds. We compared the effects of two different roasting intensities of the same naturally low-caffeine Arabica coffee variety (Laurina) on glucose and lipid metabolism as well as oxidative stress.We performed a double-blind, crossover intervention study. Fourteen healthy male volunteers consumed four cups daily of light roasted coffee (LRC) and dark roasted coffee (DRC), each for 1 wk (intervention period 1 and 2 respectively). One wk washout, with total abstinence from coffee and other possible caffeine sources, preceded each intervention. Data were collected at the end of washout and intervention periods.Changes between washout and intervention periods in glucose concentrations at 2 h post-oral glucose tolerance test, were significantly lower after DRC than LRC intake (-0.6 ± 0.3 and 0.4 ± 0.3 mmol/L, P 0.03). Changes in β-cell function, assessed as insulin secretion-sensitivity index-2, were significantly greater after DRC than LRC (34.7 ± 25.0 and -18.8 ± 21.0, P = 0.03). The initial (30 min) post-oral glucose tolerance test area under the curve of glucagon-like peptide-1 was 24± 9% greater (P = 0.03) after DRC than LRC. LRC or DRC did not affect insulin sensitivity. Changes from basal of reduced-to-oxidized glutathione ratio (GSH/GSSG) in erythrocytes were significantly greater after DRC than LRC (+1437 ± 371 and -152 ± 30, P 0.05). The omega-3 index in erythrocyte membranes was 16± 4% greater (P 0.001) after DRC than LRC.DRC consumption improved postload glucose metabolism by increasing incretin and insulin secretions. DRC compared to LRC improved redox balance and increased omega-3 fatty acids. Thus, we suggest greater metabolic benefits related to DRC.

Ageing and inactivity both contribute to systemic inflammation, but the effects of inactivity on inflammation in healthy elderly individuals have not been elucidated. We hypothesised that 14-day bed rest could affect the pro- and anti-inflammatory markers in young subjects differently than in older adults. A short-term 14-day horizontal bed rest study (BR14) has been used as a model of inactivity in two groups of healthy male volunteers: 7 aged 18-30 years (young) and 16 aged 55-65 years (older adults). The effects of inactivity on inflammation were compared. Key low-grade inflammation mediators, tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), visfatin, resistin, and anti-inflammatory adiponectin were measured in fasting serum samples, collected at baseline (BDC) and post BR14. Young responded to BR14 by increasing serum visfatin and resistin while older adults responded to BR14 by increasing IL-6 and TNF-α. In addition, serum adiponectin increased in all participants. Data from correlation analysis demonstrated positive association between Δ serum visfatin and Δ IL-6 in both groups, while Δ serum adiponectin was negatively associated with Δ TNF-α in young and positively associated with Δ resistin in the older adults. As little as 14 days of complete physical inactivity (BR14) negatively affected markers of low-grade inflammation in both groups, but the inflammation after BR14 was more pronounced in older adults. The effect of BR14 on IL-6 and resistin differed between young and older adults. Inflammatory responses to BR14 in older adults differed from those reported in the literature for obese or subjects in pathological states, suggesting potentially different mechanisms between inactivity- and obesity-induced inflammations.

Adiponectin has anti-inflammatory, antiatherosclerotic properties and it is involved in metabolic regulation, especially by sensitizing tissues for insulin. Adherence to the Mediterranean diet has been shown to have a positive effect on adiponectin levels. Therefore, our aim was to assess asymptomatic general population of the Mediterranean part of Slovenia and to evaluate the correlations between serum adiponectin levels (SALs) and diet components, dietary habits, lifestyle parameters, metabolic syndrome (MetS) components and inflammatory markers.Healthy adults aged 25-49 participated in the cross-sectional study. Linear correlation analyses were used to examine SALs on diet components, dietary habits, lifestyle parameters and all risk factors.A positive correlation between the ratio of leucine:lysine intake and adiponectin and a negative correlation between adiponectin and presence of already two components of MetS were found. Moreover, we confirmed the negative correlations between adiponectin and C-reactive protein (CRP), but found a negative correlation between adiponectin and visfatin. Furthermore, hierarchical multiple regression analyses confirmed that besides lower homeostasis model assessment insulin resistance (HOMA-IR), CRP, homocysteine and BMI, also higher ratio of leucine:lysine contributes to the prediction of higher level of adiponectin.Our results indicate that high leucine:lysine intake ratio may promote the increase in SALs in clinically asymptomatic adults. On the other hand, lower SALs are due to obesity, inflammation and presence of already 2 components of metabolic syndrome.

As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS) components in subjects prior to the onset of insulin resistance (IR). Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.