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A High-Phosphorus Diet Moderately Alters the Lipidome and Transcriptome in the Skeletal Muscle of Adult Mice

ABSTRACT: A high phosphorus intake has been associated with various metabolic disorders, including chronic kidney disease, cardiovascular disease, and osteoporosis. Recent studies have demonstrated the effects of dietary phosphorus on lipid and glucose metabolism. This study investigated the impact of a high-phosphorus diet on mouse skeletal muscle lipid composition and gene transcription. Adult male mice (n = 12/group) received either a diet with an adequate (0.3%) or a high (1.2%) phosphorus concentration for 6 weeks. The lipidome analysis showed that among the 17 analyzed lipid classes, the concentrations of three classes were reduced in the high phosphorus group compared to the adequate phosphorus group. These classes were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and lysophosphatidylcholine (LPC) (p < 0.05). Out of the three hundred and twenty-three individual lipid species analyzed, forty-nine showed reduced concentrations, while three showed increased concentrations in the high phosphorus group compared to the adequate phosphorus group. The muscle transcriptome analysis identified 142 up- and 222 down-regulated transcripts in the high phosphorus group compared to the adequate phosphorus group. Gene set enrichment analysis identified that genes that were up-regulated in the high phosphorus group were linked to the gene ontology terms “mitochondria” and “Notch signaling pathway”, whereas genes that were down-regulated were linked to the “PI3K-AKT pathway”. Overall, the effects of the high-phosphorus diet on the muscle lipidome and transcriptome were relatively modest, but consistently indicated an impact on lipid metabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE236311 | GEO | 2023/09/13

REPOSITORIES: GEO

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Project description: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.

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A High-Phosphorus Diet Moderately Alters the Lipidome and Transcriptome in the Skeletal Muscle of Adult Mice

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