To know whether isoflavones are responsible for the hypocholesterolemic effect of soy protein, the effect on plasma cholesterol of isoflavone-free soy protein prepared by column chromatography was examined in rats. Five-week-old male Sprague-Dawley rats were fed cholesterol-enriched AIN-93G diets containing either 20% casein (CAS), 20% soy protein isolate (SPI), 20% isoflavone-free SPI (IF-SPI), 19.7% IF-SPI + 0.3% isoflavone-rich fraction (isoflavone concentrate, IC), or 20% CAS + 0.3% IC for 2 weeks. Plasma total cholesterol concentrations of rats fed SPI and IF-SPI were comparable and were significantly lower than that of rats fed CAS. The addition of IC to the CAS and IF-SPI did not influence plasma cholesterol level. Fecal steroid excretion of the three SPI groups was higher than that of the two CAS groups, whereas the addition of IC showed no effect. Thus, a significant fraction of the cholesterol-lowering effect of SPI in rats can be attributed to the protein content, but the isoflavones and other minor constituents may also play a role.

BackgroundThe 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 FindingsIn 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/SignificanceWe 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.

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-Conglycinin decreased blood triacylglycerol (TAG) levels in male Wistar adult rats. Liver mitochondrial carnitine palmitoyltransferase activity in the -conglycinin-fed group significantly increased as against the casein-fed group. Hepatic fatty acid synthase activity in the -conglycinin group significantly decreased as against that of the casein-fed group. Fecal fatty acid excretion in the -conglycinin group was significantly higher than in the casein group.Key words: soybean -conglycinin; triacylglycerol (TAG); fatty acid synthase; carnitine palmitoyltransferase; fatty acid excretionIn our previous study, -conglycinin, which is one of the major components of soy protein, lowered plasma triacylglycerol (TAG) levels. 1) Moriyama et al.2) reported that -conglycinin induced -oxidation, downregulation of liver fatty acid synthase, and inhibition of TAG absorption in normal and genetically obese mice under energy restriction conditions. But it appears that more studies are necessary to explain how -conglycinin affects lipid metabolism. In this study, in order to mimic middle-aged adult humans, in whom lifestyle-related diseases occur frequently, we made an experimental design feeding a high cholesterol diet ad libitum to normal adult rats to induce dietary hyperlipidemia, and examined the effects of -conglycinin on liver lipid metabolic enzymes and fecal fat excretion to explain how -conglycinin reduces plasma TAG.All animals were treated in accordance with the guidelines established by the Japanese Society of Nutrition and Food Science (Law No. 105 and Notification No. 6 of the Japanese Government). -Conglycinin was prepared according to the method described by Saito.3) Animals, diets, and measurements were performed according to the our previous study.1) In brief, 20-week old male Wistar rats were fed experimental diets containing 20% casein or -conglycinin with free access for 10 d. Each diet contained 0.5% cholesterol and 0.125% sodium cholate, and the further components were based on the AIN-93G formula. On day 11, after 6 h of food deprivation (0730-1330), blood was withdrawn from the abdominal aorta into a heparinized syringe under intraperitoneal sodium pentobarbital anesthesia. Livers were excised, rinsed, and weighed, and then stored at À80 C pending analysis. Plasma was separated by centrifugation and stored at À80C pending analysis.All results of this study are shown in Table 1. Food consumption in the -conglycinin group increased compared with the casein group. On the other hand, there was no difference in weight gain between these groups. The plasma TAG level in the -conglycinin group was significantly lower than that in the casein group. There was no difference in plasma glucose concentration between groups. Liver weight in theconglycinin group was significantly lower than in the casein group. Hepatic carnitine palmitoyltransferase activity in the -conglycinin group was significantly higher than in the casein group. Fatty acid synthase activity in the -conglycinin group was significantly lower than th...

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Soy protein isolate (SPI) can elicit various physiological effects such as cholesterol lowering and antiobesity effects. To examine whether hepatic gene expression is altered by SPI intake, rats were fed an SPI or casein diet for 8 weeks. After 8 weeks of feeding, liver weight and plasma triglyceride and cholesterol levels were significantly lower in the SPI group than in the casein group. Hepatic gene expression was investigated using DNA microarrays. The expression profiles and statistical analysis showed clear and significant differences between the SPI and casein groups (p < 0.05); in the SPI group, 63 genes were up-regulated and 57 genes were down-regulated, most involved in various physiological functions such as lipid metabolism, antioxidant activity, transcriptional regulation, and energy metabolism. Especially in lipid metabolism, the down-regulated genes are related to fatty acid synthesis and the up-regulated genes are related to cholesterol synthesis and steroid catabolism. These results suggest that SPI intake could maintain homeostasis primarily by modulating lipid and energy metabolism.

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.