Long-Term Soy Protein Isolate Intake Reduces Liver Steatosis through Changes in Global Gene Expression in Obese Zucker Rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE158553 | GEO | 2020/11/11
REPOSITORIES: GEO
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Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.
2015-06-13 | E-GEOD-69819 | biostudies-arrayexpress
Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens.
2015-06-13 | GSE69819 | GEO
Project description:Beneficial effects of a soy diet on bone quality have been assumed to be due to the putative estrogenic actions of isoflavones. We studied the effects of soy protein isolate (SPI) on bone quality and compared these effects to 17β-estradiol (E2) in pre-pubertal rats. Female rats were weaned to a control diet with or without E2 (0.1, 1, 10 µg/kg/d), or SPI-containing diet with or without E2 (10 µg/kg/d) for 14 days beginning on postnatal day 20. In long bones from SPI-fed rats, only cancellous bone mineral density (BMD) was increased (p<0.05), while cortical BMD was decreased accompanied by lower bone strength compared to control casein-fed rats (p<0.05). In sharp contrast, 10 µg/kg/d E2 not only increased trabecular BMD, but also cortical BMD compared to controls. Rats treated with the combination of SPI and E2 had an intermediate bone effect. SPI increased while E2 decreased bone turnover, and increased trabecular BMD by both E2 and SPI was associated with decreased serum sclerostin levels. Microarray analysis revealed 652 genes regulated by SPI diet, 491 genes regulated by E2, and 266 genes regulated in common by both SPI diet and E2 compared to rats fed casein. The expression of caveolin-1, a protein localized in cell membrane, was down-regulated (p<0.05) in rats fed SPI, but not by E2 compared to rats fed casein. Down-regulated caveolin-1 by SPI was associated with increased BMP2, Smad and Runx2 expression in bone and osteoblasts (p<0.05). These results suggest SPI consumption results in significant non-classical estrogenic stimulation of cancellous bone formation prior to puberty, but may have adverse effects on overall bone quality and strength at this developmental stage as a result of reduced cortical bone formation. The study was designed to compare expression of bone development associated genes between soy protein isolate fed and estrogen treated pre pubertal female rats. Therefore, total RNA was isolated from bone from rats fed with control casein diet, SPI diet, 17 beta estrodial treated and SPI diet plus 17 beta estrodial.
2012-07-14 | E-GEOD-30862 | biostudies-arrayexpress
Project description:Beneficial effects of a soy diet on bone quality have been assumed to be due to the putative estrogenic actions of isoflavones. We studied the effects of soy protein isolate (SPI) on bone quality and compared these effects to 17β-estradiol (E2) in pre-pubertal rats. Female rats were weaned to a control diet with or without E2 (0.1, 1, 10 µg/kg/d), or SPI-containing diet with or without E2 (10 µg/kg/d) for 14 days beginning on postnatal day 20. In long bones from SPI-fed rats, only cancellous bone mineral density (BMD) was increased (p<0.05), while cortical BMD was decreased accompanied by lower bone strength compared to control casein-fed rats (p<0.05). In sharp contrast, 10 µg/kg/d E2 not only increased trabecular BMD, but also cortical BMD compared to controls. Rats treated with the combination of SPI and E2 had an intermediate bone effect. SPI increased while E2 decreased bone turnover, and increased trabecular BMD by both E2 and SPI was associated with decreased serum sclerostin levels. Microarray analysis revealed 652 genes regulated by SPI diet, 491 genes regulated by E2, and 266 genes regulated in common by both SPI diet and E2 compared to rats fed casein. The expression of caveolin-1, a protein localized in cell membrane, was down-regulated (p<0.05) in rats fed SPI, but not by E2 compared to rats fed casein. Down-regulated caveolin-1 by SPI was associated with increased BMP2, Smad and Runx2 expression in bone and osteoblasts (p<0.05). These results suggest SPI consumption results in significant non-classical estrogenic stimulation of cancellous bone formation prior to puberty, but may have adverse effects on overall bone quality and strength at this developmental stage as a result of reduced cortical bone formation.
2012-07-15 | GSE30862 | GEO
Project description:Soy foods have been suggested to have both positive health benefits and potentially adverse effects largely as a result of their content of isoflavone phytoestrogens. Since soy protein isolate (SPI) contains isoflavones, in addition to purported health benefits, safety concerns have been raised regarding the use of SPI and soy formulas, because of potential estrogenic actions during the neonatal period, including the potential for reproductive toxicity, infertility, and the possibility of increased risk for development and recurrence of estrogen sensitive cancers such as breast cancer. In the current study, we used a rat model to compare the effects of SPI with those of 17b-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were either fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND) 30.
2012-05-22 | GSE38060 | GEO
Project description:Soy foods have been suggested to have both positive health benefits and potentially adverse effects largely as a result of their content of isoflavone phytoestrogens. Since soy protein isolate (SPI) contains isoflavones, in addition to purported health benefits, safety concerns have been raised regarding the use of SPI and soy formulas, because of potential estrogenic actions during the neonatal period, including the potential for reproductive toxicity, infertility, and the possibility of increased risk for development and recurrence of estrogen sensitive cancers such as breast cancer. In the current study, we used a rat model to compare the effects of SPI with those of 17b-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were either fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND) 30. Rats were ovariectomized (OVX) on PND 50 and treated with E2 or vehicle for 14 days. Microarray analysis was carried out to compare the effects of SPI and E2 alone or in combination on the mammary gene expression. The data suggest a non-estrogenic effect of SPI on the rat mammary even in the absence of endogenous estrogens.
2012-05-21 | E-GEOD-38060 | biostudies-arrayexpress
Project description:The role of diet in the prevention of breast cancer is widely accepted, yet little is known on how early dietary effects mitigate adult cancer risk. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (GEN). We previously showed lower chemically-induced mammary tumor incidence in young adult rats with lifetime dietary intake of soy protein isolate (SPI), a highly refined soy product in infant formula, than in those fed the control diet Casein (CAS). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed CAS, SPI, or supplemental GEN-based diets. We identified mammary epithelial genes regulated by SPI (79 total) and GEN (99 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally cluster in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or GEN using QPCR. Wnt pathway inhibition by GEN was supported by lower Cyclin D1 immunoreactivity in mammary ductal epithelium of GEN relative to CAS and SPI, despite their comparable levels of membrane-localized E-cadherin and β-catenin. Identification of distinct GEN and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer. Experiment Overall Design: Female Sprague-Dawley rats, fed one of the three purified diets, were studied at postnatal day50. Total RNA( each RNA samples were extracted from #4 mammary gland from two animals under the same diet group) purified from non-tumor tissue within the proximal half of each colon, was used to prepare biotinylated probes, which were hybridized to Affymetrix RAE230 rat microarrays.
2007-11-29 | E-GEOD-6879 | biostudies-arrayexpress
Project description:We previously reported that lifetime consumption of soy proteins or whey proteins reduced the incidence of azoxymethane (AOM)-induced colon tumors in rats. To obtain insights into these effects, global gene expression profiles of colons from rats with lifetime ingestion of casein (CAS, control diet), soy protein isolate (SPI), and whey protein hydrolysate (WPH) diets were determined. We identified 31 induced and 49 repressed genes in the proximal colons of the SPI-fed group and 44 induced and 119 repressed genes in the proximal colons of the WPH-fed group, relative to CAS. Hierarchical clustering identified the co-induction or co-repression of multiple genes by SPI and WPH. The differential expression of I-FABP (2.92-, 3.97-fold down-regulated in SPI and WPH fed rats; P = 0.023, P = 0.01, respectively), cyclin D1 (1.61-, 2.42-fold down-regulated in SPI and WPH fed rats; P = 0.033, P = 0.001, respectively), and the c-neu proto-oncogene (2.46-, 4.10-fold down-regulated in SPI and WPH fed rats; P < 0.001, P < 0.001, respectively) mRNAs were confirmed by real-time quantitative RT-PCR. SPI and WPH affected colonic neuro-endocrine gene expression: peptide YY (PYY) and glucagon mRNAs were down-regulated in WPH fed rats, whereas somatostatin mRNA and corresponding circulating protein levels, were enhanced by SPI and WPH. The identification of transcripts co- or differentially-regulated by SPI and WPH diets suggests common as well as unique anti-tumorigenesis mechanisms of action which may involve growth factor, neuroendocrine and immune system genes. SPI and WPH induction of somatostatin, a known anti-proliferative agent for colon cancer cells, would inhibit tumorigenesis Experiment Overall Design: Male Sprague Dawley rats, fed one of the three purified diets, were studied at 40 weeks after AOM injection and when tumors had developed in some animals of each group. Total RNA, purified from non-tumor tissue within the proximal half of each colon, was used to prepare biotinylated probes, which were hybridized to Affymetrix RG_U34A rat microarrays.
2009-04-30 | E-GEOD-6102 | biostudies-arrayexpress
Project description:Gene expression profiles in tissues of Zucker diabetic fatty (ZDF) rats compared with age matched Zucker lean control (ZLC) rats. Keywords: other
2004-03-01 | GSE1080 | GEO
Project description:We previously reported that lifetime consumption of soy proteins or whey proteins reduced the incidence of azoxymethane (AOM)-induced colon tumors in rats. To obtain insights into these effects, global gene expression profiles of colons from rats with lifetime ingestion of casein (CAS, control diet), soy protein isolate (SPI), and whey protein hydrolysate (WPH) diets were determined. We identified 31 induced and 49 repressed genes in the proximal colons of the SPI-fed group and 44 induced and 119 repressed genes in the proximal colons of the WPH-fed group, relative to CAS. Hierarchical clustering identified the co-induction or co-repression of multiple genes by SPI and WPH. The differential expression of I-FABP (2.92-, 3.97-fold down-regulated in SPI and WPH fed rats; P = 0.023, P = 0.01, respectively), cyclin D1 (1.61-, 2.42-fold down-regulated in SPI and WPH fed rats; P = 0.033, P = 0.001, respectively), and the c-neu proto-oncogene (2.46-, 4.10-fold down-regulated in SPI and WPH fed rats; P < 0.001, P < 0.001, respectively) mRNAs were confirmed by real-time quantitative RT-PCR. SPI and WPH affected colonic neuro-endocrine gene expression: peptide YY (PYY) and glucagon mRNAs were down-regulated in WPH fed rats, whereas somatostatin mRNA and corresponding circulating protein levels, were enhanced by SPI and WPH. The identification of transcripts co- or differentially-regulated by SPI and WPH diets suggests common as well as unique anti-tumorigenesis mechanisms of action which may involve growth factor, neuroendocrine and immune system genes. SPI and WPH induction of somatostatin, a known anti-proliferative agent for colon cancer cells, would inhibit tumorigenesis Keywords: Comarative genomic hybridization
2006-10-26 | GSE6102 | GEO