Reduced postprandial energy expenditure and increased exogenous fat oxidation in young woman after ingestion of test meals with a low protein content

<p>Abstract</p> <p>Background</p> <p>Macronutrient composition of diets can influence energy balance in humans. We tested the hypothesis whether low protein content in single meals may induce lower values of energy expenditure (EE) and fat oxidation (FO) as compared to adequate protein content.</p> <p>Methods</p> <p>Indirect calorimetry was combined with a breath test using naturally ¹³C-enriched corn oil to differentiate between postprandial exogenous and endogenous FO. Young women ingested single meals containing either 3.9% (low protein, LP) or 11.4% (adequate protein, AP) of total energy (~3100 kJ) as protein.</p> <p>Results</p> <p>Postprandial EE was 160 kJ/6 h lower (p < 0.01) after LP meals and diet induced thermogenesis (DIT) increased less (p < 0.001) as compared to AP meals. Total postprandial FO was not significantly different between meals (~17 g/6 h). However, exogenous postprandial FO was significantly (p < 0.01) higher (4.28 ± 1.57 g/6 h) after exposure to LP meals as compared to AP meals (1.87 ± 1.00 g/6 h). Less than 10% of ingested fat (50 g) was oxidized in the postprandial phase. The overall postprandial fat balance was approximately + 33 g.</p> <p>Conclusion</p> <p>Breath tests using naturally ¹³C-labeled corn oil mirror exogenous FO. Low protein meals resulted in reduced postprandial EE and increased exogenous FO as compared to adequate protein meals without differences in total FO.</p

Dietary fructose in relation to blood pressure and serum uric acid in adolescent boys and girls

Evidence that fructose intake may modify blood pressure is generally limited to adult populations. This study examined cross-sectional associations between dietary intake of fructose, serum uric acid and blood pressure in 814 adolescents aged 13–15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. Energy-adjusted fructose intake was derived from 3-day food records, serum uric acid concentration was assessed using fasting blood and resting blood pressure was determined using repeated oscillometric readings. In multivariate linear regression models, we did not see a significant association between fructose and blood pressure in boys or girls. In boys, fructose intake was independently associated with serum uric acid (P<0.01), and serum uric acid was independently associated with systolic blood pressure (P<0.01) and mean arterial pressure (P<0.001). Although there are independent associations, there is no direct relationship between fructose intake and blood pressure. Our data suggest that gender may influence these relationships in adolescence, with significant associations observed more frequently in boys than girls

An Integrated Model of Multiple-Condition ChIP-Seq Data Reveals Predeterminants of Cdx2 Binding

Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS's multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions. We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2–5.National Science Foundation (U.S.) (Graduate Research Fellowship under Grant 0645960)National Institutes of Health (U.S.) (grant P01 NS055923)Pennsylvania State University. Center for Eukaryotic Gene Regulatio

American marsupials chromosomes: Why study them?

Marsupials, one of the three main groups of mammals, are only found in Australia and in the American continent. Studies performed in Australian marsupials have demonstrated the great potential provided by the group for the understanding of basic genetic mechanisms and chromosome evolution in mammals. Genetic studies in American marsupials are relatively scarce and cytogenetic data of most species are restricted to karyotype descriptions, usually without banding patterns. Nevertheless, the first marsupial genome sequenced was that of Monodelphis domestica, a South American species. The knowledge about mammalian genome evolution and function that resulted from studies on M. domestica is in sharp contrast with the lack of genetic data on most American marsupial species. Here, we present an overview of the chromosome studies performed in marsupials with emphasis on the South American species

Role of the Epigenetic Regulator HP1γ in the Control of Embryonic Stem Cell Properties

The unique properties of embryonic stem cells (ESC) rely on long-lasting self-renewal and their ability to switch in all adult cell type programs. Recent advances have shown that regulations at the chromatin level sustain both ESC properties along with transcription factors. We have focused our interest on the epigenetic modulator HP1γ (Heterochromatin Protein 1, isoform γ) that binds histones H3 methylated at lysine 9 (meH3K9) and is highly plastic in its distribution and association with the transcriptional regulation of specific genes during cell fate transitions. These characteristics of HP1γ make it a good candidate to sustain the ESC flexibility required for rapid program changes during differentiation. Using RNA interference, we describe the functional role of HP1γ in mouse ESC. The analysis of HP1γ deprived cells in proliferative and in various differentiating conditions was performed combining functional assays with molecular approaches (RT-qPCR, microarray). We show that HP1γ deprivation slows down the cell cycle of ESC and decreases their resistance to differentiating conditions, rendering the cells poised to differentiate. In addition, HP1γ depletion hampers the differentiation to the endoderm as compared with the differentiation to the neurectoderm or the mesoderm. Altogether, our results reveal the role of HP1γ in ESC self-renewal and in the balance between the pluripotent and the differentiation programs

Identification of Spt5 Target Genes in Zebrafish Development Reveals Its Dual Activity In Vivo

Spt5 is a conserved essential protein that represses or stimulates transcription elongation in vitro. Immunolocalization studies on Drosophila polytene chromosomes suggest that Spt5 is associated with many loci throughout the genome. However, little is known about the prevalence and identity of Spt5 target genes in vivo during development. Here, we identify direct target genes of Spt5 using fogsk8 zebrafish mutant, which disrupts the foggy/spt5 gene. We identified that fogsk8 and their wildtype siblings differentially express less than 5% of genes examined. These genes participate in diverse biological processes from stress response to cell fate specification. Up-regulated genes exhibit shorter overall gene length compared to all genes examined. Through chromatin immunoprecipitation in zebrafish embryos, we identified a subset of developmentally critical genes that are bound by both Spt5 and RNA polymerase II. The protein occupancy patterns on these genes are characteristic of both repressive and stimulatory elongation regulation. Together our findings establish Spt5 as a dual regulator of transcription elongation in vivo and identify a small but diverse set of target genes critically dependent on Spt5 during development

Dissecting Epigenetic Silencing Complexity in the Mouse Lung Cancer Suppressor Gene Cadm1

Disease-oriented functional analysis of epigenetic factors and their regulatory mechanisms in aberrant silencing is a prerequisite for better diagnostics and therapy. Yet, the precise mechanisms are still unclear and complex, involving the interplay of several effectors including nucleosome positioning, DNA methylation, histone variants and histone modifications. We investigated the epigenetic silencing complexity in the tumor suppressor gene Cadm1 in mouse lung cancer progenitor cell lines, exhibiting promoter hypermethylation associated with transcriptional repression, but mostly unresponsive to demethylating drug treatments. After predicting nucleosome positions and transcription factor binding sites along the Cadm1 promoter, we carried out single-molecule mapping with DNA methyltransferase M.SssI, which revealed in silent promoters high nucleosome occupancy and occlusion of transcription factor binding sites. Furthermore, M.SssI maps of promoters varied within and among the different lung cancer cell lines. Chromatin analysis with micrococcal nuclease also indicated variations in nucleosome positioning to have implications in the binding of transcription factors near nucleosome borders. Chromatin immunoprecipitation showed that histone variants (H2A.Z and H3.3), and opposing histone modification marks (H3K4me3 and H3K27me3) all colocalized in the same nucleosome positions that is reminiscent of epigenetic plasticity in embryonic stem cells. Altogether, epigenetic silencing complexity in the promoter region of Cadm1 is not only defined by DNA hypermethylation, but high nucleosome occupancy, altered nucleosome positioning, and ‘bivalent’ histone modifications, also likely contributed in the transcriptional repression of this gene in the lung cancer cells. Our results will help define therapeutic intervention strategies using epigenetic drugs in lung cancer

Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice

BACKGROUND: Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance. METHODOLOGY/PRINCIPAL FINDINGS: We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state. CONCLUSIONS/SIGNIFICANCE: The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Stable transmission of reversible modifications: maintenance of epigenetic information through the cell cycle

Even though every cell in a multicellular organism contains the same genes, the differing spatiotemporal expression of these genes determines the eventual phenotype of a cell. This means that each cell type contains a specific epigenetic program that needs to be replicated through cell divisions, along with the genome, in order to maintain cell identity. The stable inheritance of these programs throughout the cell cycle relies on several epigenetic mechanisms. In this review, DNA methylation and histone methylation by specific histone lysine methyltransferases (KMT) and the Polycomb/Trithorax proteins are considered as the primary mediators of epigenetic inheritance. In addition, non-coding RNAs and nuclear organization are implicated in the stable transfer of epigenetic information. Although most epigenetic modifications are reversible in nature, they can be stably maintained by self-recruitment of modifying protein complexes or maintenance of these complexes or structures through the cell cycle

Mechanisms and models of somatic cell reprogramming

Whitehead Institute for Biomedical Research (Jerome and Florence Brill Graduate Student Fellowship)National Institutes of Health (U.S.) (US NIH grant RO1-CA087869)National Institutes of Health (U.S.) (US NIH grant R37-CA084198)National Science Foundation (U.S.) (NSF Graduate Research Fellowship)National Institutes of Health (U.S.) ((NIH) Kirschstein National Research Service Award,1 F32 GM099153-01A1)Vertex Pharmaceuticals Incorporated (Vertex Scholar