Effect of Different Nutritional Supplements on Glucose Response of Complete Meals in Two Crossover Studies.

Postprandial hyperglycemia is an important risk factor in the development and progression of type-2 diabetes and cardiometabolic diseases. Therefore, maintaining a low postprandial glucose response is key in preventing these diseases. Carbohydrate-rich meals are the main drivers of excessive glycemic excursions during the day.

Proteomics reveals unique plasma signatures in constitutional thinness.

Purpose: Studying the plasma proteome of control versus constitutionally thin (CT) individuals, exposed to overfeeding, may give insights into weight-gain management, providing relevant information to the clinical entity of weight-gain resistant CT, and discovering new markers for the condition.

Experimental Design: Untargeted protein relative quantification of 63 CT and normal-weight individuals was obtained in blood plasma at baseline, during and after an overfeeding challenge using mass spectrometry-based proteomics.

Results: The plasma proteome of CT subjects presented limited specificity with respect to controls at baseline.

Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

Background: Constitutional thinness (CT), a non-malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free-living state. Weight and metabolic responses to protein caloric supplementation has not been yet explored in CT.

Persistent low body weight in humans is associated with higher mitochondrial activity in white adipose tissue.

Background: Constitutional thinness (CT) is a state of low but stable body weight (BMI ≤18 kg/m2). CT subjects have normal-range hormonal profiles and food intake but exhibit resistance to weight gain despite living in the modern world's obesogenic environment.

Objective: The goal of this study is to identify molecular mechanisms underlying this protective phenotype against weight gain.

Transcriptome profiling from adipose tissue during a low-calorie diet reveals predictors of weight and glycemic outcomes in obese, nondiabetic subjects.

A low-calorie diet (LCD) reduces fat mass excess, improves insulin sensitivity, and alters adipose tissue (AT) gene expression, yet the relation with clinical outcomes remains unclear. We evaluated AT transcriptome alterations during an LCD and the association with weight and glycemic outcomes both at LCD termination and 6 mo after the LCD. Using RNA sequencing (RNAseq), we analyzed transcriptome changes in AT from 191 obese, nondiabetic patients within a multicenter, controlled dietary intervention.

Role of sulfotransferases in resveratrol metabolism in human adipocytes.

Scope: Polyphenols such as resveratrol received interest for their wide-ranging biological benefits, including anti-obesity potential, mimicking effects of caloric restriction with reduced body fat and increased energy expenditure. However, resveratrol is rapidly metabolized, and it is not completely understood which form of resveratrol is responsible for the effects observed within target cells such as adipocytes. Also the role of metabolizing enzymes has not been investigated before.

Structural variation-associated expression changes are paralleled by chromatin architecture modifications.

Unlabelled: Copy number variants (CNVs) influence the expression of genes that map not only within the rearrangement, but also to its flanks. To assess the possible mechanism(s) underlying this "neighboring effect", we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. Using chromosome conformation capture (4C-seq), we observed that a set of genes flanking the Williams-Beuren Syndrome critical region (WBSCR) were often looping together.

Detecting long-range chromatin interactions using the chromosome conformation capture sequencing (4C-seq) method.

Eukaryotic transcription is tightly regulated by transcriptional regulatory elements, even though these elements may be located far away from their target genes. It is now widely recognized that these regulatory elements can be brought in close proximity through the formation of chromatin loops, and that these loops are crucial for transcriptional regulation of their target genes. The chromosome conformation capture (3C) technique presents a snapshot of long-range interactions, by fixing physically interacting elements with formaldehyde, digestion of the DNA, and ligation to obtain a library of unique ligation products.

Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.

A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region.

Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease.

The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets.

Cell-type-specific long-range looping interactions identify distant regulatory elements of the CFTR gene.

Identification of regulatory elements and their target genes is complicated by the fact that regulatory elements can act over large genomic distances. Identification of long-range acting elements is particularly important in the case of disease genes as mutations in these elements can result in human disease. It is becoming increasingly clear that long-range control of gene expression is facilitated by chromatin looping interactions.

Mapping chromatin interactions by chromosome conformation capture.

Chromosome conformation capture (3C) is one of the only techniques that allows for analysis of an intermediate level of chromosome structure ranging from a few to hundreds of kilobases, a level most relevant for gene regulation. The 3C technique is used to detect physical interactions between sequence elements that are located on the same or on different chromosomes. For instance, physical interactions between distant enhancers and target genes can be measured.

The active FMR1 promoter is associated with a large domain of altered chromatin conformation with embedded local histone modifications.

We have analyzed the effects of gene activation on chromatin conformation throughout an approximately 170-kb region comprising the human fragile X locus, which includes a single expressed gene, FMR1 (fragile X mental retardation 1). We have applied three approaches: (i) chromosome conformation capture, which assesses relative interaction frequencies of chromatin segments; (ii) an extension of this approach that identifies domains whose conformation differs from the average, which we developed and named chromosome conformation profiling; and (iii) ChIP analysis of histone modifications. We find that, in normal cells where FMR1 is active, the FMR1 promoter is at the center of a large ( approximately 50 kb) domain of reduced intersegment interactions.

Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1.

Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the beta-globin locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and the beta-major globin promoter.

Buckwheat honey increases serum antioxidant capacity in humans.

Honey has been known to exert significant in vitro antioxidant activity, in part due to its phenolic content. However, conclusions that the antioxidants in honey are or are not efficacious in the human body cannot be reached if its antioxidant action is not assessed as part of a human study. In the present study, the acute effect of consumption of 500 mL of water, water with buckwheat honey, black tea, black tea with sugar, or black tea with buckwheat honey on serum oxidative reactions was examined in 25 healthy men.

Identification and quantification of antioxidant components of honeys from various floral sources.

Little is known about the individual components of honey that are responsible for its antioxidant activity. The present study was carried out to characterize the phenolics and other antioxidants present in honeys from seven floral sources. Chromatograms of the phenolic nonpolar fraction of the honeys indicated that most honeys have similar but quantitatively different phenolic profiles.

Antioxidant capacity of honeys from various floral sources based on the determination of oxygen radical absorbance capacity and inhibition of in vitro lipoprotein oxidation in human serum samples.

Honeys from seven different floral sources were analyzed for in vitro antioxidant capacity and total phenolic content. Antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay and by monitoring the formation of conjugated dienes as an index of the inhibition of copper-catalyzed serum lipoprotein oxidation. ORAC values ranged from 3.