Circulating and adipose tissue immune cells in tissue-specific insulin resistance in humans with overweight and obesity.

Objective: A proinflammatory adipose tissue (AT) microenvironment and systemic low-grade inflammation may differentially affect tissue-specific insulin sensitivity. This study investigated the relationships of abdominal subcutaneous AT (aSAT) and circulating immune cells, aSAT gene expression, and circulating inflammatory markers with liver and skeletal muscle insulin sensitivity in people with overweight and obesity.

Methods: Individuals with overweight and obesity from the PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study (n = 219) and the Maastricht Study (replication cohort; n = 1256) underwent a seven-point oral glucose tolerance test to assess liver and muscle insulin sensitivity, and circulating inflammatory markers were determined.

Infants' Folate Markers and Postnatal Growth in the First 4 Months of Life in Relation to Breastmilk and Maternal Plasma Folate.

Background: Human milk is the sole source of folate in exclusively breastfed infants. We investigated whether human milk folate or maternal plasma folate are associated with infants' folate status and postnatal growth in the first 4 months of life.

Methods: Exclusively breastfed infants (n = 120) were recruited at age < 1 month (baseline).

Infant blood concentrations of folate markers and catabolites are modified by 5,10-methylenetetrahydrofolate reductase C677T genotype and dietary folate source.

Background: Folate intake and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may affect folate metabolism in infants.

Objectives: We investigated the association between infant's MTHFR C677T genotype, the dietary folate source, and concentrations of folate markers in the blood.

Methods: We studied 110 breastfed infants (reference) and 182 infants who were randomly assigned to receive infant formulas enriched with either 78 μg folic acid or 81 μg (6S)-5-methyltetrahydrofolate (5-MTHF) per 100 g milk powder for 12 wk.

Resveratrol and ω-3 PUFAs Promote Human Macrophage Differentiation and Function.

Monocytes differentiate into M1 and M2 macrophages, which are classically activated by microbial products such as LPS or IFN-γ and interleukins (e.g., the anti-inflammatory and T2 promoting IL-4), respectively.

Transcriptome-Wide Profile of 25-Hydroxyvitamin D in Primary Immune Cells from Human Peripheral Blood.

Vitamin D is an essential micronutrient mediating pleiotropic effects in multiple tissues and cell types via its metabolite 1α,25-dihydroxyvitamin D (1,25(OH)D), which activates the transcription factor vitamin D receptor. In this study, we used peripheral blood mononuclear cells (PBMCs) obtained from five healthy adults and investigated transcriptome-wide, whether the precursor of 1,25(OH)D, 25-hydroxyvitamin D (25(OH)D), has gene regulatory potential on its own. Applying thresholds of >2 in fold change of gene expression and <0.

Resveratrol, EGCG and Vitamins Modulate Activated T Lymphocytes.

Vitamins and bioactives, which are constituents of the food chain, modulate T lymphocyte proliferation and differentiation, antibody production, and prevent inflammation and autoimmunity. We investigated the effects of vitamins (vitamin A (VA), D (VD), E (VE)) and bioactives (i.e.

Effect of regioisomers of hydroxystearic acids as peroxisomal proliferator-activated receptor agonists to boost the anti-ageing potential of retinoids.

Introduction: We report on the in vitro and ex vivo effects of chiral (R)-10-hydroxystearic acid (10-HSA) compared with other mono-hydroxystearic acid regioisomers and stearic acid (SA) together with its benefit when combined with retinol.

Methods: Following treatment with hydroxystearic acids peroxisomal proliferator-activated receptor alpha (PPARα) activity was determined in a luciferase reporter gene assay, collagen type I was assessed in primary human dermal fibroblasts by immunohistochemistry, modification of the intracellular fibroblast collagen proteome was studied by mass-spectrometry-based proteomics and collagen type III was assessed by immunohistochemistry on human ex vivo skin.

Results: 10-HSA was the most effective PPARα agonist (15.

Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood.

Vitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)D) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.

Supplemental 25-Hydroxycholecalciferol Is More Effective than Cholecalciferol in Raising Serum 25-Hydroxyvitamin D Concentrations in Older Adults.

Background: There are few studies directly comparing the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D3] to cholecalciferol (D3).

Objectives: The primary objectives were to compare the effectiveness of D3 and 25(OH)D3 in raising 25-hydroxyvitamin D [25(OH)D] serum concentrations and achieving steady state.

Methods: This was a randomized, double-blind, active comparator trial of 91 participants (53 females, 38 males), aged 63.

Bio-derived hydroxystearic acid ameliorates skin age spots and conspicuous pores.

Introduction: We report on the preparation and efficacy of 10-hydroxystearic acid (HSA) that improves facial age spots and conspicuous pores.

Methods: The hydration of oleic acid into HSA was catalyzed by the oleate hydratase from Escherichia coli. Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1 J cm ) by immunohistochemistry on human ex vivo skin.

Large-Scale Screening of Natural Products Transactivating Peroxisome Proliferator-Activated Receptor α Identifies 9S-Hydroxy-10E,12Z,15Z-Octadecatrienoic Acid and Cymarin as Potential Compounds Capable of Increasing Apolipoprotein A-I Transcription in Human Liver Cells.

Increasing apolipoprotein A-I (apoA-I), the predominant protein of high-density lipoprotein (HDL) particles, has favorable effects on atherogenic risk factors. Here, we investigated the effects of peroxisome proliferator-activated receptor α (PPARα) transactivating compounds on apoA-I transcription in HepG2 cells. A transient PPARα agonist transactivation assay was used to screen 2500 natural compounds.

The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans.

Dietary polyphenols have beneficial effects on adipose tissue mass and function in rodents, but human studies are scarce. In a randomized, placebo-controlled study, 25 (10 women) overweight and obese humans received a combination of the polyphenols epigallocatechin-gallate and resveratrol (282 mg/d, 80 mg/d, respectively, EGCG+RES, n = 11) or placebo (PLA, n = 14) supplementation for 12 weeks. Abdominal subcutaneous adipose tissue (SAT) biopsies were collected for assessment of adipocyte morphology and micro-array analysis.

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice.

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice.

Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: the Food4Me study.

Purpose: To report the vitamin D status in adults from seven European countries and to identify behavioural correlates.

Methods: In total, 1075 eligible adult men and women from Ireland, Netherlands, Spain, Greece, UK, Poland and Germany, were included in the study.

Results: Vitamin D deficiency and insufficiency, defined as 25-hydroxy vitamin D (25-OHD) concentration of <30 and 30-49.

Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25-hydroxyvitamin D in a pan-European population: the Food4Me study.

Scope: Little is known about diet- and environment-gene interactions on 25-hydroxyvitamin D (25(OH)D concentration. This cross-sectional study aimed to investigate (i) predictors of 25(OH)D concentration and relationships with vitamin D genotypes and (ii) whether dietary vitamin D intake and sunlight exposure modified these relationships.

Methods And Results: Participants from the Food4Me study (n = 1312; age 18-79) were genotyped for vitamin D receptor (VDR) and vitamin D binding protein at baseline and a genetic risk score was calculated.

Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial.

Background: The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men.

Objective: The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity.

A 3-day EGCG-supplementation reduces interstitial lactate concentration in skeletal muscle of overweight subjects.

Green tea, particularly epigallocatechin-3-gallate (EGCG), may affect body weight and composition, possibly by enhancing fat oxidation. The aim of this double-blind, randomized placebo-controlled cross-over study was to investigate whether 3-day supplementation with EGCG (282 mg/day) stimulates fat oxidation and lipolysis in 24 overweight subjects (age = 30 ± 2 yrs, BMI = 27.7 ± 0.

Target Fishing by Cross-Docking to Explain Polypharmacological Effects.

Drugs may have polypharmacological phenomena, that is, in addition to the desired target, they may also bind to many undesired or unknown physiological targets. As a result, they often exert side effects. In some cases, off-target interactions may lead to drug repositioning or to explaining a drug's mode of action.

Vitamin D: a critical and essential micronutrient for human health.

Vitamin D is a micronutrient that is needed for optimal health throughout the whole life. Vitamin D3 (cholecalciferol) can be either synthesized in the human skin upon exposure to the UV light of the sun, or it is obtained from the diet. If the photoconversion in the skin due to reduced sun exposure (e.

Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma.

Scope: Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasing many different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites.

Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study.

Purpose: Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis. Soybean isoflavones, especially genistein, are being studied for this purpose. This study examined the effects of synthetic genistein in combination with other potential bone-protective dietary molecules on bone mineral density (BMD) in early postmenopausal women.

Nutrigenomics in human intervention studies: current status, lessons learned and future perspectives.

Nutrigenomics applications comprise transcript-, proteome- and metabolome-profiling techniques in which responses to diets or individual ingredients are assessed in biological samples. They may also include the characterization of heterogeneity in relevant genes that affect the biological processes. This review explores various areas of nutrition and food sciences in which transcriptome-, proteome- and metabolome-analyses have been applied in human intervention studies, including nutrigenetics aspects and discusses the advantages and limitations of the methodologies.

Bonistein (synthetic genistein), a food component in development for a bone health nutraceutical.

In the discussion of the risk-benefit relation of the hormone replacement therapy (HRT) for elder women phytochemicals with estrogenic activity received a great deal of attention. Phytoestrogens are naturally occurring compounds with structural similarity to 17beta-estradiol. Especially genistein, an isoflavone most abundant in soy, possess a high and selective binding-affinity to the mammalian estrogen receptors.