Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of a High Phosphorus Diet on Renal Gene Expressions in Rat

ABSTRACT: The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high-phosphorus diet. Male Wistar rats were fed a high phosphorous (HP) diet containing 1.2% phosphorous, or 0.3% HP as a control, for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with an excessive amount of the ingested phosphorus being passed through the body. DNA microarray analysis of kidney tissue from both groups revealed changes in gene expression profile induced by a HP diet. Among the genes that were upregulated, gene ontology (GO) terms related to ossification, collagen fibril organization, and inflammation and immune response were significantly enriched. In particular, there was significant upregulation of type IIb sodium-dependent phosphate transporter (NaPi-IIb) in the HP rat kidney compared to control rats. This upregulation was confirmed by in situ hybridization. Discreet signals for NaPi-IIb in both the cortex and medulla of the kidney were apparent in the HP group, while the corresponding signals were much weaker in the control group. Immunohistochemical analysis showed that NaPi-IIb localized to the basolateral side of kidney epithelial cells surrounding the urinary duct in HP rats but not in control animals. These data suggest that NaPi-IIb is upregulated in the kidney in response to the active excretion of phosphate in HP diet-fed rats. Male Wistar rats (4 weeks old) were purchased from Japan SLC Co. (Hamamatsu, Japan) and individually housed in metabolic cages under controlled conditions of 22Â±1Â°C and a 12-hour light/dark cycle (lights on from 08:00 to 20:00 daily). Two different diets containing 0.3% phosphorous (control diet) and 1.2% phosphorous (HP diet) were prepared based on the AIN-93G diet (Table 1). All rats were fed the control diet for a 7-day acclimatization period. After acclimatization, rats were divided into two groups of similar mean body weight (n = 5 each) and then fed either the control or the HP diet for 24 days. The animals were allowed to eat ad libitum and had free access to water (MilliQ water).The protocol for the animal experiments was approved by the Animal Use Committee of the Faculty of Agriculture at The University of Tokyo.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Yuji Nakai

PROVIDER: E-GEOD-31973 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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High phosphorus diet-induced changes in NaPi-IIb phosphate transporter expression in the rat kidney: DNA microarray analysis.

Suyama Tatsuya T Okada Shinji S Ishijima Tomoko T Iida Kota K Abe Keiko K Nakai Yuji Y

PloS one 20120103 1

The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high phosphorus (HP) diet. Male Wistar rats were divided into two groups and fed a diet containing 0.3% (control) or 1.2% (HP) phosphorous for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with ...[more]

PMID: 22235299

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Project description:A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid Î²-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARÎ±), a transcription factor for fatty acid Î²-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARÎ± was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARÎ± target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids released via lipolysis of white adipose tissue. Male Wistar rats (4 weeks old) were purchased from Japan SLC Co. (Hamamatsu, Japan) and individually housed in metabolic cages under controlled conditions of 22Â±1Â°C and a 12-hour light/dark cycle (lights on from 08:00 to 20:00 daily). Two different diets containing 0.3% phosphorous (control diet) and 1.2% phosphorous (HP diet) were prepared based on the AIN-93G diet (Table 1).9) All rats were fed the control diet for a 7-day acclimatization period. After acclimatization, rats were divided into two groups of similar mean body weight (n = 5 each) and then fed either the control or the HP diet for 24 days. The animals were allowed to eat ad libitum and had free access to water (MilliQ water).The protocol for the animal experiments was approved by the Animal Use Committee of the Faculty of Agriculture at The University of Tokyo. Please note that the animals used in this study are identical to those used in GSE31973.

Project description:Background: Disease severity of autosomal dominant polycystic kidney disease (ADPKD) is influenced by diet. Dietary protein, a recognized cyst-accelerating factor, is catabolized into amino acids (AA) and delivered to the kidney leading to renal hypertrophy. Injury-induced hypertrophic signaling in ADPKD results in increased macrophage (MФ) activation and inflammation followed by cyst growth. We hypothesize that the cystogenesis-prompting effects of HP diet are caused by increased delivery of specific AA to the kidney, ultimately stimulating MФs to promote cyst progression. Methods: Pkd1 flox/flox mice with and without Cre (CAGG-ER) were given tamoxifen to induce global gene deletion (Pkd1KO). Pkd1KO mice were fed either a low (LP; 6%), normal (NP; 18%), or high (HP; 60%) diet for 1 week (early) or 6 weeks (chronic). Mice were then euthanized and tissues were used for histology, immunofluorescence and various biochemical assays. One week fed kidney tissue was cell sorted to isolate tubular epithelial cells for RNA sequencing. Results: Chronic dietary protein load in Pkd1KO mice increased kidney weight, number of kidney infiltrating and resident MФs, chemokines, cytokines and cystic index compared to LP diet fed mice. Accelerated cyst growth induced by chronic HP were attenuated by liposomal clodronate-mediated MФ depletion. Early HP diet fed Pkd1KO mice had larger cystic kidneys compared to NP or LP fed counterparts, but without increases in the number of kidney MФs, cytokines, or markers of tubular injury. RNA sequencing of tubular epithelial cells in HP compared to NP or LP diet group revealed increased expression of sodium-glutamine transporter Snat3, chloride channel Clcnka, and gluconeogenesis marker Pepck1, accompanied by increased excretion of urinary ammonia, a byproduct of glutamine. Conclusion: Chronic dietary protein load-induced renal hypertrophy and accelerated cyst growth in Pkd1KO mice is dependent on both infiltrating and resident MФ recruitment and subsequent inflammatory response. Early cyst expansion by HP diet, however, is relient on increased delivery of glutamine to kidney epithelial cells, driving downstream metabolic changes prior to inflammatory provocation.

Project description:We have previously showed that whey protein hydrolysate (WPH) causes a greater increase in muscle protein synthesis than an identical composition of amino acids mixture does. The present study was conducted to investigate a comparative effect of WPH on gene expression. Male Sprague-Dawley rats subjected to a 2-h swimming exercise were administered either a carbohydrate-amino acid diet or a carbohydrate-WPH diet immediately after exercise. One hour after exercise, epitrochlearis muscle mRNA was sampled and subjected to DNA microarray analysis. As a result, ingestion of WPH altered 189 genes in considering the false discovery rate. Among the upregulated genes, 8 Gene Ontology (GO) terms were enriched, which included key elements in muscle repair after exercise such as Cd24, Ccl2, Ccl7 and Cxcl1. On the other hand, 9 GO terms were enriched in the gene sets downregulated by ingestion of WPH and these GO terms fell into 2 clusters, 'regulation of ATPase activity' and 'immune response'. Furthermore, we found that WPH activate the 2 upstream proteins, extracellular signal-regulated kinase 1/2 (ERK1/2) and hypoxia-inducible factor-1a (HIF-1a), which may act as key factors for regulation of gene expression. These results suggest that ingestion of WPH, compared to an identical composition of amino acid mixture, induces greater changes in the after-exercise gene expression profile via activation of the proteins, ERK1/2 and HIF-1a. Male Sprague-Dawley rats (5-week-old) with body weights of approximately 150 g each (CLEA Japan, Inc., Tokyo, Japan) were used in this study. Rats were maintained at 23 +/- 2C, with lights on from 8:00 to 20:00 and off from 20:00 to 8:00. Rats had free access to food (protein 23.6%, fat 5.3%, carbohydrate 54.4%, ash 6.1%, fiber 2.9%, moisture 7.7%, MF, Oriental Yeast Co., Ltd., Osaka, Japan) and water. After 2- or 3-day acclimation, the rats were pre-trained to swimming exercise for 3 days. One day before the experiment, they were fed 5 g of a restricted diet (MF, Oriental Yeast Co., Ltd., Osaka, Japan). On the day of the experiment, rats swam for 2 hours, with 4 rats swimming simultaneously in a barrel filled with water to a depth of 50 cm, allowing an average surface area of 400 cm2 for each animal. The water temperature was maintained at a constant of 35C. Immediately following exercise, rats were given one of two isoenergetic test solutions by gavage. These solutions contained 44 kJ in a four-test dose that represented about 15% of daily energy needs and included either a mixed meal containing carbohydrate and amino acid mixture (AAM) or a mixed meal containing carbohydrate and whey protein hydrolysate (WPH; Meiji Co., Ltd., Japan). This study was approved by the Animal Committee of Food Science Research Lab., Meiji Co., Ltd., with the animals receiving care according to the guidelines laid down by this committee.

Dataset Information

Effect of a High Phosphorus Diet on Renal Gene Expressions in Rat

Publications

High phosphorus diet-induced changes in NaPi-IIb phosphate transporter expression in the rat kidney: DNA microarray analysis.

Similar Datasets

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