Blood lactose after dairy product intake in healthy men.

The absence of a dedicated transport for disaccharides in the intestine implicates that the metabolic use of dietary lactose relies on its prior hydrolysis at the intestinal brush border. Consequently, lactose in blood or urine has mostly been associated with specific cases in which the gastrointestinal barrier is damaged. On the other hand, lactose appears in the blood of lactating women and has been detected in the blood and urine of healthy men, indicating that the presence of lactose in the circulation of healthy subjects is not incompatible with normal physiology. In this cross-over study we have characterised the postprandial kinetics of lactose, and its major constituent, galactose, in the serum of fourteen healthy men who consumed a unique dose of 800 g milk or yogurt. Genetic testing for lactase persistence and microbiota profiling of the subjects were also performed. Data revealed that lactose does appear in serum after dairy intake, although with delayed kinetics compared with galactose. Median serum concentrations of approximately 0·02 mmol/l lactose and approximately 0·2 mmol/l galactose were observed after the ingestion of milk and yogurt respectively. The serum concentrations of lactose were inversely correlated with the concentrations of galactose, and the variability observed between the subjects' responses could not be explained by the presence of the lactase persistence allele. Finally, lactose levels have been associated with the abundance of the Veillonella genus in faecal microbiota. The measurement of systemic lactose following dietary intake could provide information about lactose metabolism and nutrient transport processes under normal or pathological conditions

Grape polyphenols decrease circulating branched chain amino acids in overfed adults

Introduction and aims: Dietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials. Methods: Blood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov. Results: Changes in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study.Conclusion: Administration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults

Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Hyperglycaemia in diabetes mellitus (DM) alters gene expression regulation in various organs and contributes to long term vascular and renal complications. We aimed to generate novel renal genome-wide gene transcription data in rat models of diabetes in order to test the responsiveness to hyperglycaemia and renal structural changes of positional candidate genes at selected diabetic nephropathy (DN) susceptibility loci.</p> <p>Methods</p> <p>Both Affymetrix and Illumina technologies were used to identify significant quantitative changes in the abundance of over 15,000 transcripts in kidney of models of spontaneous (genetically determined) mild hyperglycaemia and insulin resistance (Goto-Kakizaki-GK) and experimentally induced severe hyperglycaemia (Wistar-Kyoto-WKY rats injected with streptozotocin [STZ]).</p> <p>Results</p> <p>Different patterns of transcription regulation in the two rat models of diabetes likely underlie the roles of genetic variants and hyperglycaemia severity. The impact of prolonged hyperglycaemia on gene expression changes was more profound in STZ-WKY rats than in GK rats and involved largely different sets of genes. These included genes already tested in genetic studies of DN and a large number of protein coding sequences of unknown function which can be considered as functional and, when they map to DN loci, positional candidates for DN. Further expression analysis of rat orthologs of human DN positional candidate genes provided functional annotations of known and novel genes that are responsive to hyperglycaemia and may contribute to renal functional and/or structural alterations.</p> <p>Conclusion</p> <p>Combining transcriptomics in animal models and comparative genomics provides important information to improve functional annotations of disease susceptibility loci in humans and experimental support for testing candidate genes in human genetics.</p

Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men

The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers

The postprandial metabolome — a source of Nutritional Biomarkers of Health

The novel concept of 'Nutritional Biomarkers of Health' (NBH) is introduced in this paper. In analogy to glucose, metabolites in blood that (i) respond postprandially to the ingestion of foods, (ii) differentiate healthy individuals from individuals with metabolic diseases under fasting and/or postprandial conditions, and (iii) have plausible mechanisms that associate them with metabolic diseases, may qualify as NBHs. The use of metabolomics to link food composition to the metabolic status of a subject after ingestion offers a unique approach for the identification of NBHs and thus, the discovery and development of dietary solutions that prevent disease and promote health

Decreasing Insulin Sensitivity in Women Induces Alterations in LH Pulsatility

Context: Obesity is associated with neuroendocrine reproductive alterations and decreased fertility. Objective: The objective of the study was to gain insight into the neuroendocrine mechanisms implicated in these alterations. Design: The effects on pulsatile LH secretion of 28 days of a hypercaloric diet were studied in lean and regularly cycling female volunteers. Approximately 50% extra calories (3 g sucrose/kg body weight per day and 1 g fat/kg body weight per day) were added to their individual daily requirements. Spontaneous and insulin-stimulated LH secretion was recorded on 2 different days, before and at the end of the caloric load. Results: The hypercaloric diet induced an average weight gain of 2.0 ± 0.3 kg (P < .05), corresponding to a body mass index increase of 0.7 ± 0.1 kg/m2 (P < .05). A concomitant decrease of 11.6% ± 4.6% in whole-body insulin sensitivity was also observed (δ = −1.6 ± 0.7 mg/kg · min glucose; P < .05). The frequency of spontaneous and insulin-stimulated pulsatile LH secretion was increased by 17.9% ± 9.0% and 26.5% ± 9.0%, respectively (both P < .05). Spontaneous LH peak amplitude was decreased by 26.5% ± 9.0% (δ = −0.7 ± 0.36 U/L; P < .05), a change correlated with insulin sensitivity. Conclusions: Short-term weight gain in normal female volunteers induces alterations of LH secretion reminiscent to those observed in obesity. A decrease in insulin sensitivity may constitute a mechanistic link between obesity and its associated neuroendocrine dysfunctions

A quantitative trait locus influencing type 2 diabetes susceptibility maps to a region on 5q in an extended French family.

Type 2 diabetes is a heterogeneous disorder of glucose metabolism characterized by insulin resistance, beta-cell dysfunction, and increased glucose production by the liver. Given the high degree of genetic heterogeneity, multiple genes with small to moderate effects may influence susceptibility to diabetes. To circumvent this limitation, we searched for quantitative trait loci (QTLs) that explain the variation in susceptibility of type 2 diabetes in a single extended family, as these individuals are likely to share polymorphisms. We collected genotypic and phenotypic data on 152 individuals ascertained through a multimedia campaign in France to find diabetes-prone families for genetic studies. The effects of genes and covariates (age and sex) on diabetes status were estimated using a threshold model and a maximum likelihood variance component approach. We obtained suggestive evidence of linkage (logarithm of odds [LOD] = 2.4) for diabetes status on chromosome 5q. Within the 1-LOD unit support interval, there are two strong candidates: PCSK1 and CAST. Furthermore, we have obtained a replication (LOD = 1.6) for a QTL for type 2 diabetes on chromosome 11 detected by Hanson and colleagues (1998)