Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism.

There is growing interest in the potential health benefits of diets that involve regular periods of fasting. While animal studies have provided compelling evidence that feeding patterns such as alternate-day fasting can increase longevity and reduce incidence of many chronic diseases, the evidence from human studies is much more limited and equivocal. Additionally, although several candidate processes have been proposed to contribute to the health benefits observed in animals, the precise molecular mechanisms responsible remain to be elucidated. The study described here examined the effects of an extended fast on gene transcript profiles in peripheral blood mononuclear cells from ten apparently healthy subjects, comparing transcript profiles after an overnight fast, sampled on four occasions at weekly intervals, with those observed on a single occasion after a further 24 h of fasting. Analysis of the overnight fasted data revealed marked inter-individual differences, some of which were associated with parameters such as gender and subject body mass. For example, a striking positive association between body mass index and the expression of genes regulated by type 1 interferon was observed. Relatively subtle changes were observed following the extended fast. Nonetheless, the pattern of changes was consistent with stimulation of fatty acid oxidation, alterations in cell cycling and apoptosis and decreased expression of key pro-inflammatory genes. Stimulation of fatty acid oxidation is an expected response, most likely in all tissues, to fasting. The other processes highlighted provide indications of potential mechanisms that could contribute to the putative beneficial effects of intermittent fasting in humans.

Effect of a mixture of bovine milk oligosaccharides, Lactobacillus rhamnosus NCC4007 and long-chain polyunsaturated fatty acids on catch-up growth of intra-uterine growth-restricted rats.

AIM: To investigate the effect of a nutritional mixture (bovine milk oligosaccharides, Lactobacillus rhamnosus NCC4007, arachidonic and docosahexaenoic acid) on growth of intrauterine growth-restricted (IUGR) rats. METHODS: IUGR was induced by maternal food restriction. The offspring (males and females) were assigned to: REF (non-IUGR, no mixture), IUGRc (IUGR, no mixture), or IUGRmx (IUGR, mixture). The mixture was given from day 7 to day 58, when tissues and plasma from half of the animals were collected for hormones, metabolites and microarray analysis. The rest received a high-fat diet (HFD) until day 100. Glucose tolerance was measured at 56 and 98 days, and body fat content at 21, 52 and 97 days. RESULTS: IUGRmx had the greatest growth during lactation, but from day 22 to day 54, both IUGR groups gained less body weight than the REF (P < 0.05). In the short-term (58 days), IUGRmx tended to be longer (P = 0.06) and had less body fat (P = 0.03) than IUGRc. These differences were not seen after HFD. Microarray analysis of hepatic mRNA expression at 58 and 100 days revealed a gender-dependent treatment effect, and expression of genes related to lipid metabolism was the most affected. Twelve of these genes were selected for studying differences in DNA methylation in the promoter region, for some, we observed age- and gender-related differences but none because of treatment. CONCLUSION: The nutritional intervention promoted catch-up growth and normalized excessive adiposity in IUGR animals at short-term. The benefits did not extend after a period of HFD. IUGR and early diet had gender-dependent effects on hepatic gene expression.

Peptide transporters and their roles in physiological processes and drug disposition.

1. The peptide transporters belong to the peptide transporter (PTR) family and serve as integral membrane proteins for the cellular uptake of di- and tripeptides in the organism. By their ability also to transport peptidomimetics and other substrates with therapeutic activities or precursors of pharmacologically active agents, they are of considerable importance in pharmacology. 2. PEPT1 is the low-affinity, high-capacity transporter and is mainly expressed in the small intestine, whereas PEPT2 is the high-affinity, low-capacity transporter and has a broader distribution in the organism. 3. Targeted mouse models have revealed PEPT2 to be the dominant transporter for the reabsorption of di- and tripeptides and its pharmacological substrates in the organism, and for the removal of these substrates from the cerebrospinal fluid. Moreover, the peptide transporters undergo physiological and pharmacological regulation and, of great interest, are present in disease states where PEPT1 exhibits ectopic expression in colonic inflammation. 4. The paper reviews the structural characteristics of the peptide transporters, the structural requirements for substrates, the distribution of the peptide transporters in the organism, and finally their regulation in the organism in healthy and pathological situations.

Cloning and characterization of the gene encoding the mouse peptide transporter PEPT2.

Here we describe the cDNA structure, genomic organization, chromosomal localization, and promoter analysis of the mouse peptide transporter PEPT2. The PEPT2-cDNA is 3987 bp long and encodes a protein of 729 amino acids. The functional properties, analyzed by expression in Xenopus laevis oocytes, showed a typical PEPT2-phenotype with electrogenic, proton-coupled transport, high substrate affinity, and a broad specificity. Immunoblotting of renal brush-border membranes revealed an apparent molecular mass of PEPT2 of 100 kDa. The murine Pept2 gene was cloned from a 129/SvevTACfBr genomic library. It is 34 kb long and comprises 22 exons and 21 introns. By radiation mapping analysis the Pept2 gene was mapped on central mouse chromosome 16. Two putative transcription start sites lying 35 and 235 bp upstream from the translation start were identified. The Pept2 gene possesses a TATA-less promoter. Functional promoter analysis revealed the core promoter to be located between 432 and 286 bp upstream from the translation start.

Vitamin C status of adults living in Valencia, Spain. Influence of non-nutritional factors on plasma vitamin C.

Ascertaining the antioxidant nutritional status of different population groups is of great interest because of the probable benefits of these nutrients in the prevention of chronic disease. In this study the vitamin C status of adults living in a region characterized by its high availability of food with a high vitamin C content was investigated. In addition, vitamin C intake and the effect of non-nutritional factors on plasma vitamin C was examined. The majority of the subjects had an adequate vitamin C status. Nevertheless, by a probabilistic method it was established that a large proportion of the population was at risk of consuming inadequate amounts of vitamin C, the risk being considerably higher among male smokers. Females had higher vitamin C plasma concentrations than men. This difference persisted after adjusting the data for smoking habits. Also women's vitamin C intake was higher. Smoking affected male's plasma vitamin C concentrations negatively. Neither age nor the season of data collection had an effect on plasma vitamin C. Vitamin C intake was only influenced by season among males. No factor affected significantly vitamin C intake or plasma vitamin concentrations among females. Finally, multiple linear regression analysis showed that vitamin C intake and smoking habits make it possible to predict, in part, plasma vitamin C concentrations in males.