Sodium butyrate protects against oxidative stress in high-fat-diet-induced obese rats by promoting GSK-3ß/Nrf2 signaling pathway and mitochondrial function.

Sodium butyrate (NaB), obtained by fermenting dietary fiber via intestinal microflora, was recently shown to improve the activity of some antioxidant enzymes in vivo. This study aims to investigate the term changes of mitochondrial energy metabolism and redox homeostasis in skeletal muscles and clarify the regulatory mechanism and dose effect of NaB on skeletal muscle. Male Sprague-Dawley rats were divided into the control group, obesity-prone (OP) group and obesity-resistant (OR) group based on the gain of body weight after 8 weeks' of feeding high-fat diet (HFD), followed by sacrificing rats at the end of 20th week. NaB intervention (12 weeks) could effectively reduce the body weight of rats in the OP and OR groups. NaB also mediated upregulation of antioxidant enzyme activity and GSH/GSSG ratio, while reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. At the molecular level, NaB upregulated Pi3k, Nrf2, Nqo-1, and Ho-1, but downregulated Gsk-3ß mRNA expression by regulating the Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention significantly upregulated Glut4, Irs-1, Pdx1, and MafA, expression in gastrocnemius muscles of OP and OR rats, and elevated insulin secretion and muscle insulin sensitivity. Thus, NaB activates antioxidant pathway, improves the antioxidant capacity of obese rat tissues and promotes glucose metabolism. PRACTICAL APPLICATIONS: This study found that obesity-prone and obesity-resistant rats have differences in mitochondrial redox homeostasis and energy metabolism in tissues. Meanwhile, sodium butyrate can effectively promote muscle protein synthesis, increase insulin sensitivity, and promote glucose metabolism in obesity rats. Thus, sodium butyrate supplementation or increasing intestinal butyrate production (e.g., by consuming foods rich in dietary fiber) is a potential means of improving the body's glucose metabolism and obesity profile.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.

BACKGROUND: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. RESULTS: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. CONCLUSIONS: The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.

Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Agaricomycetidae), Derived Polysaccharides Exert Immunomodulatory Activities In Vitro and In Vivo.

The royal sun mushroom, Agaricus brasiliensis is a widely consumed mushroom around the world. In this study, the immunoregulatory potential of A. brasiliensis polysaccharides was investigated in vitro and in vivo. In vivo, the polysaccharides remarkably increased the spleen and thymus indexes in mice, and this effect was influenced significantly by age (the adult and the juvenile). The spleen index increased by 27.28% in adult mice treated with the polysaccharides, whereas the increase in juvenile mice was just 12.59% at the dose of 150 mg·kg-1·d-1. Moreover, the effect of the polysaccharides on the thymus and spleen indexes in adult mice was obvious both in males and females. The carbon clearance ability (phagocytic index) was improved with increasing doses, (32.81% at 120 mg·kg-1·d-1, and 38.34% at 150 mg·kg-1·d-1) in mice treated with the polysaccharides. In vitro, the polysaccharides increased the RAW264.7 cell proliferation with 34.78% at 25 µg/mL and 26.78% at 50 µg/mL. Furthermore, the polysaccharides also promoted mRNA expressions of interleukin (IL)-6, IL-1ß, cyclooxygenase-2, and Toll-like receptor 4 (TLR4), myeloid differentiation 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-ß (TRIF) in the cells, indicating that the polysaccharides induce the secretion of inflammatory cytokines by stimulating TLR4/MyD88 and TLR4/TRIF pathways. In conclusion, these results suggest that A. brasiliensis polysaccharides induce a very promising immunostimulation effect in vivo and in vitro. Therefore, it should be explored as a novel natural functional food additive.

Genome sequencing of the high oil crop sesame provides insight into oil biosynthesis.

BACKGROUND: Sesame, Sesamum indicum L., is considered the queen of oilseeds for its high oil content and quality, and is grown widely in tropical and subtropical areas as an important source of oil and protein. However, the molecular biology of sesame is largely unexplored. RESULTS: Here, we report a high-quality genome sequence of sesame assembled de novo with a contig N50 of 52.2 kb and a scaffold N50 of 2.1 Mb, containing an estimated 27,148 genes. The results reveal novel, independent whole genome duplication and the absence of the Toll/interleukin-1 receptor domain in resistance genes. Candidate genes and oil biosynthetic pathways contributing to high oil content were discovered by comparative genomic and transcriptomic analyses. These revealed the expansion of type 1 lipid transfer genes by tandem duplication, the contraction of lipid degradation genes, and the differential expression of essential genes in the triacylglycerol biosynthesis pathway, particularly in the early stage of seed development. Resequencing data in 29 sesame accessions from 12 countries suggested that the high genetic diversity of lipid-related genes might be associated with the wide variation in oil content. Additionally, the results shed light on the pivotal stage of seed development, oil accumulation and potential key genes for sesamin production, an important pharmacological constituent of sesame. CONCLUSIONS: As an important species from the order Lamiales and a high oil crop, the sesame genome will facilitate future research on the evolution of eudicots, as well as the study of lipid biosynthesis and potential genetic improvement of sesame.

Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1.

Functional pancreatic neuroendocrine tumours (PNETs) are mainly represented by insulinoma, which secrete insulin independent of glucose and cause hypoglycaemia. The major genetic alterations in sporadic insulinomas are still unknown. Here we identify recurrent somatic T372R mutations in YY1 by whole exome sequencing of 10 sporadic insulinomas. Further screening in 103 additional insulinomas reveals this hotspot mutation in 30% (34/113) of all tumours. T372R mutation alters the expression of YY1 target genes in insulinomas. Clinically, the T372R mutation is associated with the later onset of tumours. Genotyping of YY1, a target of mTOR inhibitors, may contribute to medical treatment of insulinomas. Our findings highlight the importance of YY1 in pancreatic ß-cells and may provide therapeutic targets for PNETs.

Whole genome DNA methylation analysis based on high throughput sequencing technology.

There are numerous approaches to decipher a whole genome DNA methylation profile ("methylome"), each varying in cost, throughput and resolution. The gold standard of these methods, whole genome bisulfite-sequencing (BS-seq), involves treatment of DNA with sodium bisulfite combined with subsequent high throughput sequencing. Using BS-seq, we generated a single-base-resolution methylome in human peripheral blood mononuclear cells (in press). This BS-seq map was then used as the reference methylome to compare two alternative sequencing-based methylome assays (performed on the same donor of PBMCs): methylated DNA immunoprecipitation (MeDIP-seq) and methyl-binding protein (MBD-seq). In our analysis, we found that MeDIP-seq and MBD-seq are complementary strategies, with MeDIP-seq more sensitive to highly methylated, high-CpG densities and MDB-seq more sensitive to highly methylated, moderate-CpG densities. Taking into account the size of a mammalian genome and the current expense of sequencing, we feel 3gigabases (Gbp) 45bp paired-end MeDIP-seq or MBD-seq uniquely mapped reads is the minimum requirement and cost-effective strategy for methylome pattern analysis.

Ancient human genome sequence of an extinct Palaeo-Eskimo.

We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.