Effects of a Diet Containing Sources of Prebiotics and Probiotics and Modification of the Gut Microbiota on the Reduction of Body Fat.

In 2022, according to the World Health Organization (WHO) report, overweight and obesity have reached epidemic proportions in the WHO European Region, affecting almost 60% of adults. Based on the assessment of BMI (Body Mass Index), a group of 56 women aged 25-45 years (31 women group A average BMI 34.9 ± 4.86 kg/m2 and 25 women group B average BMI 33.4 ± 4.02 kg/m2) were qualified for the study. In a multi-center, two-arm, parallel, non-randomized study, two types of weight-reduction diets (A and B) were used over a 3-month period. In group A, a standard low-energy diet was used with individually adjusted caloric intake of 1100-1300 kcal, with an increase in the amount and frequency of consumption of sauerkraut and groats and a daily intake of fermented milk drinks (300-400 g), fermented cucumbers (100 g), mineral water (1 L) and cod liver oil (5 mL). In group B, a standard low-energy diet with individually adjusted caloric intake of 1100-1300 kcal with daily intake of fermented milk products (150 g), highly mineralized water (0.5 L), once a week fermented cucumbers, and once a week buckwheat groats was used. The following measurements were taken: body weight, body fat mass, water content, body height, waist circumference, and hip circumference. Body weight and body composition were measured using the Tanita MC-780 MA and TANITA BC-601 analyzer using the bioelectric bioimpedance method. The stool samples were analyzed in the microbiology laboratory where quantification of Bifidobcaterium spp., Bacteroides spp., Faecalibacterium prausnitzii species, Akkermansia muciniphila and total bacterial count (TBC) was performed. Under the influence of the introduced nutritional intervention, a statistically significant reduction in body weight, body fat, waist circumference, and hip circumference was demonstrated after 3 months. Under the influence of weight reduction, as well as dietary changes, there was an increase in the number of Akkermansia muciniphila bacteria in the women studied. The low-energy diet containing sources of natural prebiotics and probiotics had a more favorable effect on the number of Faecalibacterium prausnitzii bacteria compared to the standard diet.

New Succinimides with Potent Anticancer Activity: Synthesis, Activation of Stress Signaling Pathways and Characterization of Apoptosis in Leukemia and Cervical Cancer Cells.

Based on previously identified dicarboximides with significant anticancer and immunomodulatory activities, a series of 26 new derivatives were designed and synthesized by the Diels-Alder reaction between appropriate diene and maleimide or hydroxymaleimide moieties. The resulting imides were functionalized with alkanolamine or alkylamine side chains and subsequently converted to their hydrochlorides. The structures of the obtained compounds were confirmed by 1H and 13C NMR and by ESI MS spectral analysis. Their cytotoxicity was evaluated in human leukemia (K562, MOLT4), cervical cancer (HeLa), and normal endothelial cells (HUVEC). The majority of derivatives exhibited high to moderate cytotoxicity and induced apoptosis in K562 cells. Microarray gene profiling demonstrated upregulation of proapoptotic genes involved in receptor-mediated and mitochondrial cell death pathways as well as antiapoptotic genes involved in NF-kB signaling. Selected dicarboximides activated JNK and p38 kinases in leukemia cells, suggesting that MAPKs may be involved in the regulation of apoptosis. The tested dicarboximides bind to DNA as assessed by a plasmid DNA cleavage protection assay. The selected dicarboximides offer new scaffolds for further development as anticancer drugs.

Novel Benzo[B]Furans with Anti-Microtubule Activity Upregulate Expression of Apoptotic Genes and Arrest Leukemia Cells in G2/M Phase.

BACKGROUND: Novel derivatives of benzo[b]furan were found to be highly toxic towards human chronic myelogenous (K562), acute myelogenous (HL-60) and acute lymphoblastic (MOLT-4) leukemia cells. OBJECTIVE: The objective was the characterization of the biological activity of novel benzofurans (influence on apoptosis, mitogen-activated protein kinases and on the cell cycle). Cellular protein(s) targeted by test benzofurans and mechanism of action were identified. METHODS: The methods utilized in the study were chemical synthesis, fluorescence assays, flow cytometry, gene expression by DNA microarray and real-time RT-PCR, western blotting, cytotoxicity assays, pull-down assay, mass spectroscopy, in vitro polymerization of tubulin, molecular docking. RESULTS: 1,1'-[3-(bromomethyl)-5,6- dimethoxy-1-benzofuran-2,7-diyldiethanone (1) and methyl 4-bromo-6- (dibromoacetyl)-5-hydroxy-2-methyl-1-benzofuran-3-carboxylate (2) induced apoptosis in K562 and MOLT-4 cells. The profiling of gene expression revealed that 1 and 2 increased the expression of proapoptotic genes involved in both receptor (TNFRSF 10A, TNFRSF 10B, CASP8) and mitochondrial (BAX, BID, NOXA, APAF1) pathways of apoptosis. Test benzo[b]furans activated c-Jun N-terminal kinase (JNK) and p38 kinase in K562 cells. Tubulin was identified as a protein target for benzo[b]furans in pull-down experiments with biotinylated 2. Test benzo[b]furans inhibited polymerization of tubulin monomers in vitro, decreased the level of cellular microtubules and arrested cells in a G2/M phase. Molecular docking suggests that benzo[b]furans 1 and 2 bind to tubulin via colchicine binding pocket and the complex is stabilized mainly by hydrophobic interactions. CONCLUSION: Novel benzo[b]furans with anti-microtubule activity were identified. They induce apoptosis in cancer cells and cause G2/M cell cycle arrest. Biological activity of 1 and 2 makes them potential lead compounds for development as anticancer drugs.

Effect of caloric restriction on liver function in young and old ApoE/LDLr-/- mice

Background: Caloric restriction (CR) leads to decrease metabolic intensity, which results in a reduction of oxygen consumption and the amount of free radicals. This can affect the function of the liver. Studies show that caloric restriction does not alter or significantly increase the enzyme activity associated with gluconeogenesis, but the effect was different according to the age of the model animals. Objective: The aim of the study was to determine the effect of caloric restriction on liver function in young and old ApoE/ LDLr-/- mice. Material and methods: Dietary experiments were performed on 2 and 5 month old male ApoE/LDLr-/- mice. Animals were divided into 3 experimental groups (n=6) and fed AIN'93G diet for 8 and 5 weeks, respectively. Control animals were fed ad libitum (AL) and housed in a colony cages. These animals were checked for dietary intake. The second group were also fed ad libitum but the animals were kept individually in cages (stress AL- sAL). Similarly to sAL group, the animals from the CR group were kept individually but received a 30% less diet compared to AL group. At the end of the experiment animals were euthanized and the blood, liver and adipose tissue have been collected. Alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST) were measured in plasma. Fatty acid profile was evaluated (relative %) in adipose tissue (GC-MS). Liver's stetosis was assessed. Results were analyzed statistically (ANOVA, STATISTICA v.10.0). Results: CR ApoE/LDLr-/- mice showed significantly lower body weight compared to animals, both AL and sAL. There were no significant differences between ALT and AST in both younger and older animals. However, negative tendencies were more pronounced in younger animals. In young animals CR significantly increased liver weight compared to AL (4.14 vs 3.73g/100g). In adipose tissue fatty acid profile differed in CR mice compared to control in young animals. Conclusions: Caloric restriction did not affect liver enzymes in mice. Caloric restriction showed similar but not identical metabolic activity in young and old mice.

Effects of nanoporous anodic titanium oxide on human adipose derived stem cells.

The aim of current bone biomaterials research is to design implants that induce controlled, guided, successful, and rapid healing. Titanium implants are widely used in dental, orthopedic, and reconstructive surgery. A series of studies has indicated that cells can respond not only to the chemical properties of the biomaterial, but also, in particular, to the changes in surface topography. Nanoporous materials remain in focus of scientific queries due to their exclusive properties and broad applications. One such material is nanostructured titanium oxide with highly ordered, mutually perpendicular nanopores. Nanoporous anodic titanium dioxide (TiO2) films were fabricated by a three-step anodization process in propan-1,2,3-triol-based electrolyte containing fluoride ions. Adipose-derived stem cells offer many interesting opportunities for regenerative medicine. The important goal of tissue engineering is to direct stem cell differentiation into a desired cell lineage. The influence of nanoporous TiO2 with pore diameters of 80 and 108 nm on cell response, growth, viability, and ability to differentiate into osteoblastic lineage of human adipose-derived progenitors was explored. Cells were harvested from the subcutaneous abdominal fat tissue by a simple, minimally invasive, and inexpensive method. Our results indicate that anodic nanostructured TiO2 is a safe and nontoxic biomaterial. In vitro studies demonstrated that the nanotopography induced and enhanced osteodifferentiation of human adipose-derived stem cells from the abdominal subcutaneous fat tissue.

Association of single nucleotide polymorphism rs7579169 with hypertension disorders during pregnancy and perinatal outcome.

BACKGROUND: Hypertension during pregnancy is a heterogeneous group of disorders with elevated blood pressure with or without proteinuria. The multiple researches are held on the subject of a genetic conditioning of preeclampsia and pregnancy induced hypertension. OBJECTIVES: The study was designed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7579169 on hypertension disorders in pregnancy, especially on PE and PIH as well as on the perinatal outcome. METHODS: It is a case-control study. The study included 104 women with uncomplicated pregnancies in the control group and 75 pregnant women with hypertension disorders in the study group, hospitalized in the Perinatology and Obstetrics Department of the University Hospital in Cracow. Genomic DNA was extracted from peripheral blood leukocytes and SNP rs7579169 was genotyped from all patients. We analyzed the genotypes distribution and allele frequencies of polymorphism rs7579169 and its association with perinatal outcome in all groups. A p-value<0.05 was considered as significant. RESULTS: Clinical evaluation included standard anthropometric measures like weight and height for the calculation of the body mass index in the beginning and in the end of the pregnancy, blood pressure, time and a method of delivery, birth weight, Apgar score. The heterozygote CT was associated with a 4.5-fold increased risk of preeclampsia in pregnant patients. The presence of TT genotype significantly increased the risk of intrauterine growth restriction (<10 percentile). CONCLUSIONS: The study show probable impact of SNP rs7579169 on pregnancy, but further studies on larger groups are needed.

Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count.

INTRODUCTION: Centrifugation is an essential step for plasma preparation to remove residual elements in plasma, especially platelets and platelet-derived microparticles (PMPs). Our working hypothesis was that centrifugation as a preanalytical step may influence some coagulation parameters. MATERIALS AND METHODS: Healthy young men were recruited (N=17). For centrifugation, two protocols were applied: (A) the first centrifugation at 2500xg for 15 min and (B) at 2500xg for 20 min at room temperature with a light brake. In protocol (A), the second centrifugation was carried out at 2500xg for 15 min, whereas in protocol (B), the second centrifugation involved a 10 min spin at 13,000 x g. Thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes concentrations were determined by enzyme-linked immunosorbent assays. PMPs were stained with CD41 antibody and annexin V, and analyzed by flow cytometry method. Procoagulant activity was assayed by the Calibrated Automated Thrombogram method as a slope of thrombin formation (CAT velocity). RESULTS: Median TAT and PAP concentrations did not differ between the centrifugation protocols. The high speed centrifugation reduced the median (IQR) PMP count in plasma from 1291 (841-1975) to 573 (391-1010) PMP/µL (P=0.001), and CAT velocity from 2.01 (1.31-2.88) to 0.97 (0.82-1.73) nM/min (P=0.049). Spearman's rank correlation analysis showed correlation between TAT and PMPs in the protocol A plasma which was (rho=0.52, P<0.050) and between PMPs and CAT for protocol A (rho=0.74, P<0.050) and protocol B (rho=0.78, P<0.050). CONCLUSION: Centrifugation protocols do not influence the markers of plasminogen (PAP) and thrombin (TAT) generation but they do affect the PMP count and procoagulant activity.

A novel TAZ gene mutation and mosaicism in a Polish family with Barth syndrome.

Barth syndrome (BTHS) is an X-linked recessive disease primarily affecting males. Clinically, the disease is characterized by hypertrophic or dilated cardiomyopathy, skeletal myopathy, chronic/cyclic neutropenia, 3-methylglutaconic aciduria, growth retardation and respiratory chain dysfunction. It is caused by mutations in the TAZ gene coding for the tafazzin protein which is responsible for cardiolipin remodeling. In this work, we present a novel pathogenic TAZ mutation c.83T>A, p.Val28Glu, found in mosaic form in almost all female members of a Polish family. Sanger sequencing of DNA from peripheral blood and from epithelial cells showed female mosaicism in three generations. This appears to be a new mechanism of inheritance and further research is required in order to understand the mechanism of this mosaicism. We conclude that BTHS genetic testing should include two or more tissues for women that appear to be noncarriers when blood DNA is initially tested. The results of our study should not only be applicable to BTHS families, but also to families with other X-linked diseases.

Gold-oxoborate nanocomposites and their biomedical applications.

A novel inorganic nanocomposite material, called BOA, which has the form of small building blocks composed of gold nanoparticles embedded in a polyoxoborate matrix, is presented. It is demonstrated that cotton wool decorated with the BOA nanocomposite displays strong antibacterial activity toward both Gram-positive and -negative bacteria strains. Importantly, the modified cotton does not release any toxic substances, and the bacteria are killed upon contact with the fibers coated with the BOA. Toxicity tests show that the nanocomposite--in spite of its antiseptic properties--is harmless for mammalian cells. The presented method of surface modification utilizes mild, environmentally friendly fabrication conditions. Thus, it offers a facile approach to obtain durable nontoxic antiseptic coatings for biomedical applications.

[DNA methylation in obesity]. / Metylacja DNA a otylosc prosta.

The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes), have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA) synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described.

Apoptosis-related gene expression in glioblastoma (LN-18) and medulloblastoma (Daoy) cell lines.

The expression of apoptosis genes in a commercial pre-designed low-density array from Applied Biosystems was evaluated in two human brain cancer cell models, LN-18 and Daoy (HTB-186™) in comparison to the reference human primary endothelial cells under basic conditions. Analysis of the gene expression in the cancer cell lines compared to the normal control revealed features reflecting anti-apoptotic and inflammatory characteristics of the former. There was an overall downregulation of apoptosis-stimulating genes in both cancer cell lines, along with an upregulation of certain apoptosis inhibitors. A number of genes demonstrated statistically significant changes in their expressions, including BAX (BCL2-associated X protein); the CARD4/NLR family, CARD domain containing 4; CASP10 (caspase 10, apoptosis-related cysteine peptidase); DAP1 (death-associated protein kinase 1), and BIRC5 (baculoviral IAP repeat-containing 5). Anti-apoptotic potential in both cell lines was demonstrated by changes in the Bax:Bcl-2 ratio and downregulation of the APAF1 gene in LN18 cells. There was also significant downregulation of extrinsic signals and the TNF/FADD/inflammatory cascade, and upregulation of caspase inhibitors (IAPs). These results provided a novel molecular characterization of important human cancer cell lines, which might provide a useful research tool for investigating the experimental model of the CNS cell.

Number of microparticles generated during acute myocardial infarction and stable angina correlates with platelet activation.

BACKGROUND AND AIMS: Elevated levels of circulating microparticles (MPs) have been reported in patients with acute myocardial infarction (AMI) and coronary artery disease. Platelet activation and inflammation have been recognized during AMI and stable angina (SA). We hypothesize that the origin and count of MPs in AMI and SA patients are related to markers of inflammation and platelet activation. METHODS: Platelet, monocytes and endothelial MPs and surface P-selectin were determined in 12 AMI patients, 10 SA patients and 9 controls by flow cytometry. Plasma P-selectin, CD40 ligand (sCD40L) and interleukin 6 (IL-6) levels were evaluated by ELISA methods. RESULTS: The total MP count was compared in control subjects, AMI, and SA patients: 12,765 (8465) vs. 38,750 (11,931) vs. 29,715 (12,072) counts/µl (p = 0.01), respectively. Patients with AMI displayed higher levels of total and platelet origin- tissue factor-positive (CD42/CD142) MPs than patients with SA: 72.8 (6.2) vs. 56.2 (6.4) %, p = 0.001. Levels of soluble P-selectin were significantly elevated in patients with AMI as compared to SA patients: 146 (6.5) vs. 107 (2.7) ng/mL, p = 0.005; significant correlation between total MP count and relative number of CD34, CD51, CD42-positive MPs, and the P-selectin expression was observed in patients with AMI. CONCLUSIONS: Platelet activation in AMI is associated with increased generation of MPs not only from platelets, but also monocytes and endothelial cells. It suggests that interactions between platelets, monocytes and endothelial cells play an important role in the pathogenesis of myocardial ischemia.

[Humanin and its derivatives as peptides with potential antiapoptotic and confirmed neuroprotective activities]. / Humanina i jej analogi jako peptydy o potencjalnym dzialaniu antyapoptotycznym i potwierdzonych wlasciwosciach neuroprotekcyjnych.

Humanin (HN) is a newly discovered 24-amino acid peptide, which may suppress neuronal cell death. HN cDNA includes the open reading frame (HN-ORF) of 75 bases, located 950 bases downstream of the 5' end of the HN cDNA. It was demonstrated that HN cDNA is 99% identical with mitochondrial DNA (mtDNA) sequence. HN homologues have been identified as expressed sequence tags (ESTs) in rat and nematode. Certain regions homologous to the HN cDNA exist on human chromosomes. HN forms homodimers and multimers and this seems to be essential for the peptide functions. HN acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). It was demonstrated that HN plays a protective role by an antiapoptotic activity interfering with Bax activation, and suppressing Bax-dependent apoptosis. HN is also shown to suppress the c-Jun N-terminal kinase (JNK) and ASK/JNK-mediated neuronal cell death. Several studies also confirm that HN could be important in prevention of angiopathy-associated Alzheimer's disease dementia, diseases related to mitochondrial dysfunction (MELAS), and other types of beta-amyloid accumulation associated neurodegeneration. A very recent study demonstrated a pluripotent cytoprotective effect and mechanisms of HNs in cells other than from the CNS, such as germ cells, or panreatic b-cells, and potent physiological consequences that result from HN interaction with IGFBP3 and STAT3. The in vivo studies suggest that humanin may protect against cognitive impairment, also due to ischemia/reperfusion injury.

Role of microRNAs in endothelial cell pathophysiology.

MicroRNAs (miRNAs) are a family of small, noncoding RNAs that repress gene expression at the post-transcriptional level. Over 700 miRNAs have been identified in the human genome, of which 20% to 30% regulate human protein-coding genes. Functional in vitro studies have shown that miRNAs are critical for endothelial cell gene expression and function. miRNAs were found in atherosclerosis, cardiac hypertrophy, arterial hypertension, coronary artery disease, diabetes, and inflammatory diseases. We review the current knowledge about the role of miRNAs in endothelial cells with emphasis on the regulation of cellular senescence, angiogenesis, and vascular inflammation. It has been shown that miR-34a, miR-217, miR-200, miR-146c, and miR-181a are responsible for the regulation of cell stress and proliferation processes. Proangiogenic factors include miR-130a, miR-210, miR-424, miR-17-92, miR-27-b, let-7f, and miR-217, while miR-221 and miR-222 have antiangiogenic properties. Other known miRNAs, including miR-31, miR17-3p, miR-155, miR-221, miR-222, and miR-126, are important factors in the regulation of vascular inflammation. Studies show that miRNA expression analysis can be used in the diagnosis and treatment of various diseases; however, additional research is needed before it is used in routine clinical setting.

Humanins, the neuroprotective and cytoprotective peptides with antiapoptotic and anti-inflammatory properties.

Humanin (HN) is a newly discovered 24-amino acid peptide, which may suppress neuronal cell death. HN cDNA includes an open reading frame (HN-ORF) of 75 bases located 950 bases downstream of the 5' end of the HN cDNA. It has been demonstrated that HN cDNA is 99% identical to the mitochondrial DNA (mtDNA) sequence. HN homologs have been identified as expressed sequence tags (ESTs) in both rats and nematodes. Certain regions that are homologous to the HN cDNA exist on human chromosomes. HN forms homodimers and multimers and this action seems to be essential for peptide function. HN acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). It has been demonstrated that HN plays a protective role through its antiapoptotic activity that interferes with Bax activation, which suppresses Bax-dependent apoptosis. HN has also been shown to suppress the c-Jun N-terminal kinase (JNK) and ASK/JNK-mediated neuronal cell death. Several studies have also confirmed that HN could be important in the prevention of angiopathy-associated Alzheimer's disease dementia, diseases related to mitochondrial dysfunction (MELAS), and other types of ß-amyloid accumulation-associated neurodegeneration. Avery recent study demonstrated a pluripotent cytoprotective effect and mechanisms of HNs in cells not from the CNS, such as germ cells or pancreatic ß-cells, and the potent physiological consequences that result from HN interaction with IGFBP3 and STAT3. In vivo studies suggest that HN may also protect against cognitive impairment due to ischemia/reperfusion injury.

[Variants of adiponectin gene as risk factors for the metabolic syndrome]. / Warianty genu adiponektyny jako czynniki ryzyka zespolu metabolicznego.

Adiponectin, a protein secreted by adipose tissue but present at low levels in obesity, is now widely recognized as a key determinant of insulin sensitivity and of protection against obesity-associated metabolic syndrome. The adiponectin gene is very polymorphic and several of its variants contribute to adiponectin level, function and are associated with metabolic syndrome phenotypes. The results differ ethnically. The association of identified variants with obesity and its consequences, type 2 diabetes and cardiovascular disease is reviewed. This data may enable patients at greater risk of the adverse effects of obesity to be identified and, as such, benefit from more targeted therapy and prevention.

Nutrigenomic approaches for benefit-risk analysis of foods and food components: defining markers of health.

To be able to perform a comprehensive and rigorous benefit-risk analysis of individual food components, and of foods, a number of fundamental questions need to be addressed first. These include whether it is feasible to detect all relevant biological effects of foods and individual food components, how such effects can confidently be categorised into benefits and risks in relation to health and, for that matter, how health can be quantified. This article examines the last of these issues, focusing upon concepts for the development of new biomarkers of health. Clearly, there is scope for refinement of classical biomarkers so that they may be used to detect even earlier signs of disease, but this approach defines health solely as the absence of detectable disease or disease risk. We suggest that the health of a biological system may better be reflected by its ability to withstand and manage relevant physiological challenges so that homeostasis is maintained. We discuss the potential for expanding the range of current challenge tests for use in conjunction with functional genomic technologies to develop new types of biomarkers of health.

Evaluation of genetic predisposition to insulin resistance by nutrient-induced insulin output ratio (NIOR).

BACKGROUND: New tools to identify genotype-phenotype interactions need to be described and implemented. The aim of this study was to identify correlation between the risk originating from gene variation and diet-dependent development of insulin resistance. METHODS: Insulin output in terms of area under the curve after an oral glucose tolerance test (AUC Ins OGTT) and lipid tolerance tests (AUC Ins OLTT) were measured in 167 overweight/obese patients. Estimation of the 18 common gene polymorphisms for obesity risk and standard phenotyping were performed. RESULTS: Insulin output (AUC Ins OGTT) correlated strongly between both insulin treatments across the whole group. However, within the genotype sub-groups, correlation was lower or did not exist. Using a nutrient-induced insulin output ratio (NIOR), calculated as AUC Ins OLTT/AUC Ins OGTT, values ranged from 0.42 to 5.83 and correlated significantly with body mass index (BMI) and leptin, but not with age, gender, waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) or plasma adiponectin. High NIOR was found in a subgroup of carriers of rare allelic variants of genes characteristic for poorer tolerance to lipids in the diet. Low NIOR values were found within a sub-group with rare genetic variants regulating carbohydrate metabolism. Thus, the new insulin index NIOR may distinguish gene variant carriers into groups of glucose- or lipid-sensitive phenotypes. CONCLUSIONS: We suggest that the OLTT/OGTT insulin output ratio (NIOR) may be predictive for identifying individuals who are phenotypically susceptible to insulin resistance in response to high fat or carbohydrate in their habitual diet.

Nutrient-gene interactions in benefit-risk analysis.

Individuals respond differently to nutrients and foods. This is reflected in different levels of benefits and risks at the same intake of a nutrient and, consequently, different 'windows of benefit' in terms of nutrient intake. This has led recently to the concept of 'personalised nutrition'. Genetic factors such as single nucleotide polymorphisms may be one source of this inter-individual variation in benefit-risk response to nutrients. In 2004 a European Union-funded network of excellence in the area of nutrigenomics (European Nutrigenomics Organisation; NuGO) organised a workshop on the role of nutrient-gene interactions in determining benefit-risk of nutrients and diet. The major issues discussed at the workshop are presented in the present paper and highlighted with examples from the presentations. The overall consensus was that although genetics provides a new vision where genetic information could in the future be used to provide knowledge on disease predisposition and nutritional requirements, such a goal is still far off and much more research is required before we can reliably include genetic factors in the risk-benefit assessment of nutrients and diets.

Genetic Aspects of Obesity.

The paper reviews recent problems in understanding of the genetic basis and gene/gene, as well as gene/environment interaction in the development of obesity and its complications.