Nobuhiko Tachibana

Effects of Soybean β-Conglycinin on Hepatic Lipid Metabolism and Fecal Lipid Excretion in Normal Adult Rats

β-Conglycinin decreased blood triacylglycerol (TAG) levels in male Wistar adult rats. Liver mitochondrial carnitine palmitoyltransferase activity in the β-conglycinin-fed group significantly increased as against the casein-fed group. Hepatic fatty acid synthase activity in the β-conglycinin group significantly decreased as against that of the casein-fed group. Fecal fatty acid excretion in the β-conglycinin group was significantly higher than in the casein group.

β-Conglycinin Lowers Very-Low-Density Lipoprotein-Triglyceride Levels by Increasing Adiponectin and Insulin Sensitivity in Rats

The relationship between insulin sensitivity and the plasma triglyceride-lowering effect induced by β-conglycinin was investigated. Male Wistar rats (19 weeks old) were fed diets containing casein, soy protein isolate, or β-conglycinin for 4 weeks. In oral glucose administration, the β-conglycinin-fed rats showed a significant decrease in the area under the glucose curve (0–60 min) as compared with the casein-fed rats. The hypoglycemic effect was significantly higher in the β-conglycinin-fed rats than in the casein-fed rats at 30 min after intraperitoneal insulin injection. The liver sterol regulatory element-binding-protein-1 mRNA expression level was significantly lower and the plasma adiponectin concentration was significantly higher in the β-conglycinin-fed rats than in the casein-fed rats. The hypotriglyceridemic effect of β-conglycinin depended on a significant decrease in the concentration of very-low-density-lipoprotein triglycerides. These results indicate that β-conglycinin increases adiponectin levels and improves glucose tolerance. The ability of β-conglycinin to lower plasma lipid levels might be due to increased insulin sensitivity of the liver.

Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

Background The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. Methodology/Principal Findings In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. Conclusions/Significance We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina.

Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats

BackgroundDietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats.MethodsIn Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3.ResultsNo observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration.ConclusionsThese results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.

Soybean β-conglycinin improves carbohydrate and lipid metabolism in Wistar rats.

The effects of dietary soybean β-conglycinin on lipid metabolism and energy consumption were studied in Wistar adult rats. Rats were fed, a diet containing casein (control group) or β-conglycinin (β-conglycinin group), for 4 weeks. Carbohydrate consumption was higher and fat consumption was lower in the β-conglycinin group than in the control group, whereas the total energy consumption was the same between the two groups. Serum adiponectin was higher in the β-conglycinin group than in the control group. Serum triacylglycerol levels in the β-conglycinin group were significantly lower than those in the control group. The secretion rate of triacylglycerols from the liver after the administration of tyloxapol, an inhibitor of lipolysis, was significantly lower in the β-conglycinin group than in the control group. These results suggest the possibility that β-conglycinin exerts hypolipidemic effects through an acceleration in carbohydrate consumption associated with an increase in adiponectin in rats. Graphical abstract β-Conglycinin, compared to casein, accelerated carbohydrate and protein consumption and suppressed fat consumption in rats. This can be a mechanism of hypolipidemic effects of β-conglycinin.

Temporal profiling of photoreceptor lineage gene expression during murine retinal development

Rod and cone photoreceptors are photosensitive cells in the retina that convert light to electrical signals that are transmitted to visual processing centres in the brain. During development, cones and rods are generated from a common pool of multipotent retinal progenitor cells (RPCs) that also give rise to other retinal cell types. Cones and rods differentiate in two distinct waves, peaking in mid-embryogenesis and the early postnatal period, respectively. As RPCs transition from making cones to generating rods, there are changes in the expression profiles of genes involved in photoreceptor cell fate specification and differentiation. To better understand the temporal transition from cone to rod genesis, we assessed the timing of onset and offset of expression of a panel of 11 transcription factors and 7 non-transcription factors known to function in photoreceptor development, examining their expression between embryonic day (E) 12.5 and postnatal day (P) 60. Transcription factor expression in the photoreceptor layer was observed as early as E12.5, beginning with Crx, Otx2, Rorb, Neurod1 and Prdm1 expression, followed at E15.5 with the expression of Thrb, Neurog1, Sall3 and Rxrg expression, and at P0 by Nrl and Nr2e3 expression. Of the non-transcription factors, peanut agglutinin lectin staining and cone arrestin protein were observed as early as E15.5 in the developing outer nuclear layer, while transcripts for the cone opsins Opn1mw and Opn1sw and Recoverin protein were detected in photoreceptors by P0. In contrast, Opn1mw and Opn1sw protein were not observed in cones until P7, when rod-specific Gnat1 transcripts and rhodopsin protein were also detected. We have thus identified four transitory stages during murine retina photoreceptor differentiation marked by the period of onset of expression of new photoreceptor lineage genes. By characterizing these stages, we have clarified the dynamic nature of gene expression during the period when photoreceptor identities are progressively acquired during development.

Effects of Soy Protein Isolate Feeding on Severe Kidney Damage in DOCA Salt-Treated Obese Zucker Rats

This study assessed the effects of soy protein isolate (SPI) on severe kidney damage in deoxycorticosterone acetate (DOCA) salt-treated obese Zucker rats. These rats underwent heminephrectomy and were fed either casein or SPI diet for 12 weeks. From weeks 8 to 10 of the experiment, kidney damage was induced by biweekly injection of 25 mg/kg DOCA and administration of 0.5% NaCl (w/v) ad libitum. Urinary protein and N-acetyl-β-d-glucosaminidase excretions of SPI rats were much lower than those of casein rats at weeks 1 (p < 0.01) and 2 (p < 0.05) after DOCA treatment. Abnormal mineral excretions induced by DOCA treatment in casein rats were hardly detected in SPI rats. Severe atrophy of tubular epithelium and some flattened/detached renal tubules were also observed in casein rats, but not in SPI rats. These results indicate that consecutive treatment of SPI protects against renal dysfunction, particularly tubulointerstitial nephritis, in DOCA salt-treated obese Zucker rats.

Dietary soybean protein ameliorates high-fat diet-induced obesity by modifying the gut microbiota-dependent biotransformation of bile acids

The consumption of soybean protein has well-known favorable metabolic effects (e.g., reduced body weight, body fat, hyperglycemia, insulin resistance, hepatic steatosis, and lipogenesis). These effects of soy protein have been linked to modulation by the gut microbiota; however, the dynamic interplay among these factors remains unclear. Accordingly, we examined the metabolic phenotype, intestinal BA pool, and the gut microbiome of male C57BL/6 mice that were randomized to receive either a regular high-fat diet (HFD) or HFD that contained soybean protein isolate (SPI) in place of dairy protein. The intake of SPI significantly reduced the HFD-induced weight gain and adipose tissue mass accumulation and attenuated hepatic steatosis. Along with an enhancement in the secretion of intestinal Glucagon-like peptide-1 (GLP-1), an enlarged cecal BA pool with an elevated secondary/primary BA ratio was observed in the mice that consumed SPI, while fecal BA excretion remained unaltered. SPI also elicited dramatic changes in the gut microbiome, characterized by an expansion of taxa that may be involved in the biotransformation of BAs. The observed effects were abolished in germ-free (GF) mice, indicating that they were dependent on the microbiota. These findings collectively indicate that the metabolic benefits of SPI under the HFD regime may arise from a microbiota-driven increase in BA transformation and increase in GLP-1 secretion.

Hamartoma-like lesions in the mouse retina: an animal model of Pten hamartoma tumour syndrome

ABSTRACT PTEN hamartoma tumour syndrome (PHTS) is a heterogeneous group of rare, autosomal dominant disorders associated with PTEN germline mutations. PHTS patients routinely develop hamartomas, which are benign tissue overgrowths comprised of disorganized ‘normal’ cells. Efforts to generate PHTS animal models have been largely unsuccessful due to the early lethality of homozygous germline mutations in Pten, together with the lack of hamartoma formation in most conditional mutants generated to date. We report herein a novel PHTS mouse model that reproducibly forms hamartoma-like lesions in the central retina by postnatal day 21. Specifically, we generated a Pten conditional knockout (cKO) using a retinal-specific Pax6::Cre driver that leads to a nearly complete deletion of Pten in the peripheral retina but produces a mosaic of ‘wild-type’ and Pten cKO cells centrally. Structural defects were only observed in the mosaic central retina, including in Müller glia and in the outer and inner limiting membranes, suggesting that defective mechanical integrity partly underlies the hamartoma-like pathology. Finally, we used this newly developed model to test whether rapamycin, an mTOR inhibitor that is currently the only PHTS therapy, can block hamartoma growth. When administered in the early postnatal period, prior to hamartoma formation, rapamycin reduces hamartoma size, but also induces new morphological abnormalities in the Pten cKO retinal periphery. In contrast, administration of rapamycin after hamartoma initiation fails to reduce lesion size. We have thus generated and used an animal model of retinal PHTS to show that, although current therapies can reduce hamartoma formation, they might also induce new retinal dysmorphologies. This article has an associated First Person interview with the first author of the paper. Summary: The authors present the first PHTS animal model that successfully recapitulates hamartoma formation in the retina and can be used to assess drug therapies.

Accelerating effect of soy peptides containing collagen peptides on type I and III collagen levels in rat skin.

Two weeks of feeding soy peptides containing 2% collagen peptides increased the levels of type I and III tropocollagen and their mRNAs. In contrast, the diet did not increase the mRNA levels of rat hyaluronan synthases, serine palmitoyltransferase (the rate-limiting enzyme of ceramide synthesis), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the key enzyme of cholesterol synthesis). These results suggest that feeding of soy peptides with collagen peptides specifically enhanced the tropocollagen level in the skin.