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Ichikawa, D.

Publications and source records attributed to Ichikawa, D..

2 recordsLinked to original sources

Hexanoic acid improves metabolic health in mice fed high-fat diet.

BackgroundOverweight and obesity is currently a worldwide problem with undesirable health consequences such as type 2 diabetes. Therefore, much attention has been paid to preventing obesity through diet. Free fatty acids (FFAs) are an important energy source, and they also serve as signaling molecules in many biological processes leading to an increased energy expenditure and insulin secretion. Short-chain fatty acids (SCFAs) such as acetic, propionic and butyric acid are the bioactive metabolites produced by gut microbes, and their beneficial effects on host metabolism are well-studied. In addition, medium-chain fatty acids (MCFAs) such as octanoic and decanoic acid also play a positive role in regulating lipid and glucose metabolisms. However, the effects of hexanoic acid on metabolism are poorly understood. Therefore, this study investigated the role of hexanoic acid on lipid and glucose metabolism in mice. MethodsMale C57BL/6J mice were fed normal chow diet, high-fat diet (HFD), HFD-containing 5% butyric acid or HFD-containing 5% hexanoic acid for 4 weeks, and the effects of hexanoic acid on lipid and glucose metabolism were examined. ResultsButyric acid and hexanoic acid prevented body weight gain and fat accumulation in white adipose tissues under HFD-feeding. In addition, both FFAs suppressed the elevated plasma levels of non-esterified fatty acid (NEFA) and hepatic triglyceride content induced by HFD. The expression levels of genes involved in fatty acid biosynthesis were decreased in white adipose tissues by oral supplementation of butyric acid or hexanoic acid. Mice fed HFD also exhibited hyperglycemia and hyperinsulinemia, and these impaired glucose metabolisms improved by hexanoic acid. Hexanoic acid increased the expression levels of genes associated with gluconeogenesis, and improved insulin sensitivity in mice fed HFD. ConclusionsThis study highlights the importance of hexanoic acid in improvement of lipid and glucose metabolisms. Thus, our findings provide insight into the development of functional foods which prevent obesity-related disease such as type 2 diabetes.

physiology↗

Manipulating the 3D organization of the largest synthetic yeast chromosome

Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field, especially when the synthetic genomes are extensively modified with thousands of designer features. Here we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp Saccharomyces cerevisiae chromosome resulting from extensive genome streamlining and modification. During the construction of synIV, we developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction and facilitated chromosome debugging. In addition to the drastic sequence changes made to synIV by rewriting it, we further manipulated the three-dimensional structure of synIV in the yeast nucleus to explore spatial gene regulation within the nuclear space. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of the largest synthetic yeast chromosome shed light on higher-order architectural design of the synthetic genomes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/487066v2_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@18bf586org.highwire.dtl.DTLVardef@1a471d5org.highwire.dtl.DTLVardef@12d7690org.highwire.dtl.DTLVardef@1c32510_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDe novo synthesis of the largest eukaryotic chromosome, synIV C_LIO_LISynIV shows similar 3D structure to wild-type IV, despite thousands of changes made to it C_LIO_LI"Inside-out" repositioning of synIV in nucleus shows minor transcriptional changes C_LIO_LIMultipoint tethering synIV to inner nuclear membrane represses transcription of whole chromosome C_LI

synthetic biology↗