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 forage conservation method on ruminal lipid metabolism and microbial ecology in lactating cows fed diets containing a 60:40 forage-to-concentrate ratio.

The effect of forage conservation method on ruminal lipid metabolism and microbial ecology was examined in 2 complementary experiments in cows. Treatments comprised fresh chopped grass, barn-dried hay, or untreated (UTS) or formic acid-treated silage (FAS) prepared from the same grass sward. Preparation of conserved forages coincided with the collection of samples from cows offered fresh grass. In the first experiment, 5 multiparous Finnish Ayrshire cows (229 d in milk) were used to compare the effects of feeding diets based on grass followed by hay during 2 consecutive 14-d periods separated by a 5-d transition during which extensively wilted grass was fed. In the second experiment, 5 multiparous Finnish Ayrshire cows (53 d in milk) were assigned to 1 of 2 blocks and allocated treatments according to a replicated 3×3 Latin square design with 14-d periods to compare the effects of hay, UTS, and FAS. Cows received 7 or 9 kg/d of the same concentrate in experiments 1 and 2, respectively. Conservation of grass by drying, but not ensiling, decreased forage fatty acid content primarily due to losses of 18:2n-6 and 18:3n-3. Compared with grass, feeding hay had no effect on dry matter intake (DMI), rumen pH, or fermentation characteristics, other than increasing ammonia content, but lowered whole-tract organic matter and fiber digestibility (experiment 1). Relative to hay, silage increased DMI, rumen volatile fatty acid (VFA) concentrations, and molar proportions of butyrate, and decreased molar acetate proportions (experiment 2). Compared with UTS, FAS increased DMI, had no effect on rumen ammonia or VFA concentrations, but tended to lower rumen pH and the molar ratio of lipogenic to glucogenic VFA. Conservation method had no substantial effect on ruminal or whole-tract digestibility coefficients. Compared with fresh grass and silages, hay decreased lipolysis and biohydrogenation (BH) of dietary unsaturates in the rumen, resulting in similar flows of 18:2n-6 and 18:3n-3, but lower amounts of trans-11 18:1 and Δ11,13 18:2 at the omasum. The extent of silage fermentation had minimal influence on ruminal lipid metabolism. Treatments were not associated with changes in the relative abundance of specific bacteria known to be capable of BH or rumen protozoal numbers. In conclusion, conservation method altered forage lipids, the extent of lipolysis and BH in the rumen, and the flow of fatty acids at the omasum, in the absence of substantial changes in ruminal Butyrivibrio populations.

Differential regulation of expression of cytosolic and mitochondrial thioredoxin reductase in rat liver and kidney.

Adequate supply of selenium (Se) is critical for synthesis of selenoproteins through selenocysteine insertion mechanism. To explore this process we investigated the expression of the cytosolic and mitochondrial isoenzymes of thioredoxin reductase (TrxR1 and TrxR2) in response to altered Se supply. Rats were fed diets containing different quantities of selenium and the levels of TrxR1 and TrxR2 protein and their corresponding mRNAs were determined in liver and kidney. Expression of the two isoenzymes was differentially affected, with TrxR1 being more sensitive to Se depletion than TrxR2 and greater changes in liver than kidney. In order to determine if the selenocysteine incorporation sequence (SECIS) element was critical in this response liver and kidney cell lines (H4 and NRK-52E) were transfected with reporter constructs in which expression of luciferase required read-through at a UGA codon and which contained either the TrxR1 or TrxR2 3'UTR, or a combination of the TrxR1 5' and 3'UTRs. Cell lines expressing constructs with the TrxR1 3'UTR demonstrated no response to restricted Se supply. In comparison the Se-deficient cells expressing constructs with the TrxR2 3'UTR showed considerably less luciferase activity than the Se-adequate cells. No disparity of response to Se supply was observed in the constructs containing the different TrxR1 5'UTR variants. The data show that there is a prioritisation of TrxR2 over TrxR1 during Se deficiency such that TrxR1 expression is more sensitive to Se supply than TrxR2 but this sensitivity of TrxR1 was not fully accounted for by TrxR1 5' or 3'UTR sequences when assessed using luciferase reporter constructs.

Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males: influences of smoking.

OBJECTIVE: To quantify the major carotenoids in plasma of Scottish males and establish which were affected by habitual smoking. DESIGN: Concentrations of carotenoids, vitamin C and vitamin E (alpha and gamma-tocopherol) were determined in plasma samples from 50 fasted male smokers and 50 age-matched males who had never smoked (aged 50-59 years). RESULTS: Significantly less alpha-carotene, beta-carotene and beta-cryptoxanthin and vitamin C in plasma of smokers than in never-smokers whereas concentrations of lycopene, lutein/zeaxanthin, phytofluene and vitamin E were similar between the groups. CONCLUSION: Whether lower carotenoid and vitamin C concentrations in smokers than never-smokers reflect different dietary patterns or increased metabolic turnover is unclear but smokers may benefit from increased carotenoid and vitamin C intakes.