Squalene modulates fatty acid metabolism: Enhanced EPA/DHA in obese/diabetic mice (KK-A(y)) model

Biosynthesis of long-chain n-3 fatty acids from precursors is limited. In vivo effect of squalene (SQ) on the metabolic fate of n-3 fatty acid precursors in obese/diabetic KK-A(y) rodent model was evaluated in our work. Soybean oil, being rich in ALA (18:3 n-3; a known precursor of EPA/DHA), was chosen as the n-3 fatty acid precursor rich source. A high-fat diet (20%) containing 7% soybean oil (SO) was fed to obesity/diabetes-prone male KK-A(y) mice (control). In the case of diets fed to test groups, soybean oil was replaced with 5% SO and 2% SQ. Hepatic DHA levels increased (four fold) in SQ fed group over control (p<0.05). Gene and protein expressions of (5) and (6) desaturases, key enzymes involved in the fatty acid metabolism, further supported the results. Also, SQ exhibited a hypotriglyceridemic and hypoglycemic effect. The results clearly indicated the effect of SQ in modulating the n-3 fatty acid metabolism, including EPA/DHA synthesis in the presence of n-3 fatty acid precursor. This is the first report of enhancement of in vivo DHA/EPA by SQ and in turn, modulating the physiological fatty acid profile. Practical applications: Squalene (SQ) is an important marine biofunctional material that is found in some terrestrial sources as well. Squalene, being a cholesterol precursor, forms an interesting subject of research for its effect in vivo. SQ significantly enhanced proportions of EPA and/or DHA when their n-3 fatty acid precursors were available in the diet. The study further establishes the usefulness of SQ in functional food formulations. The work provides an important basis for further evaluation of the role of SQ in normal and disease conditions.KK-A(y) mice were fed high fat/sucrose diet to induce obesity/diabetes. Fat source in control diet was lard and soybean oil while experimental group diet contained 2% squalene+13% lard+5% soybean oil. Feeding squalene for 4weeks modulated fatty acid metabolism with increased docosahexaenoic acid (DHA) and decrease in triglycerides (TG), compared to control. The enhanced DHA in the fatty acid profile was supported by upregulated mRNA expression of (5)-desaturase enzyme and protein expression of (5) and (6) desaturases (FADS1 and FADS2). Additionally, squalene had a hypoglycemic effect in the mice

Comparison of Oxidative Stability of Monogalactosyl Diacylglycerol, Digalactosyl Diacylglycerol, and Triacylglycerol Containing Polyunsaturated Fatty Acids

Oxidative stability of three different lipid classes, namely, monogalactosyl diacylglycerol (MGDG) and digalactosyl diacylglycerol (DGDG) from spinach and edible brown seaweed (Akamoku) and triacylglycerol (TAG) of linseed oil was compared. Analysis of oxygen consumption and polyunsaturated fatty acid (PUFA) composition demonstrated that spinach DGDG had the highest oxidative stability, followed by Akamoku DGDG, Akamoku MGDG, spinach MGDG, and linseed TAG. These results disagree with the order of oxidative stability expected from the average number of bis-allylic positions of each lipid. Additionally, DGDG constituents of both spinach and Akamoku showed higher oxidative stability than their MGDG constituents. The unusual oxidative stability of MGDG and DGDG could be conferred by the protection of bis-allylic positions of the PUFA against oxidative attack by the galactosyl moiety of the GL

シガケン ナガハマシ ホウゲン ノ ソザイ タイグウ ケイシキ ニ カンスル キジュツテキ ケンキュウ

The isomerization of n-hexadecane over Pt–WO3 catalysts supported on TiO2–SiO2 synthesized by glycothermal reaction with various Si/Ti molar ratios was examined. The catalyst performance depended on Si/Ti molar ratio and WO3 loading. The characterization of the catalysts by XRD, XAFS, UV-vis and so on revealed that with increasing the WO3 loading, the structure of surface W species changed from monomeric species to polytungstate species, which is considered to significantly affect the isomerization selectivity of the catalysts

Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes

Background: Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated. Results: To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis. Conclusions: Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains.ArticleBMC GENOMICS. 14:248 (2013)journal articl

Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in acquired aplastic anemia

Idiopathic aplastic anemia (AA) is a common cause of acquired BM failure. Although autoimmunity to hematopoietic progenitors is thought to be responsible for its pathogenesis, little is known about the molecular basis of this autoimmunity. Here we show that a substantial proportion of AA patients harbor clonal hematopoiesis characterized by the presence of acquired copy number-neutral loss of heterozygosity (CNN-LOH) of the 6p arms (6pLOH). The 6pLOH commonly involved the HLA locus, leading to loss of one HLA haplotype. Loss of HLA-Aexpression from multiple lineages of leukocytes was confirmed by flow cytometry in all 6pLOH(+) cases. Surprisingly, the missing HLAalleles in 6pLOH(+) clones were conspicuously biased to particular alleles, including HLA-A*02:01, A*02:06, A*31:01, and B*40:02. A large-scale epidemiologic study on the HLA alleles of patients with various hematologic diseases revealed that the 4 HLA alleles were over-represented in the germline of AA patients. These findings indicate that the 6pLOH(+) hematopoiesis found in AA represents "escapes"hematopoiesis from the autoimmunity, which is mediated by cytotoxic T cells that target the relevant autoantigens presented on hematopoietic progenitors through these class I HLAs. Our results provide a novel insight into the genetic basis of the pathogenesis of AA. © 2011 by The American Society of Hematology

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article