Renal transcriptome changes in testosterone deficient-pigs fed a high-fat diet
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ABSTRACT:
PROVIDER: PRJNA515895 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR8456194.fastq.gz | Fastqsanger.gz | |||
| SRR8456195.fastq.gz | Fastqsanger.gz | |||
| SRR8456196.fastq.gz | Fastqsanger.gz | |||
| SRR8456197.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Obesity and dyslipidemia are associated with increased risk of renal disease.Testosterone deficiency aggravated high-fat diet-induced obesity and hypercholeterolemia. However,whether testosterone deficiency or testosterone deficiency-induced dyslipidemia aggravate the progression of renal disease is not clear. To gain insight into the role of testosterone in modulating renal lipid metabolism, we profiled renal gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT). Methods: Sexually mature male miniature pigs were either surgical castrated or sham-operated, and castrated with testosterone replacement. We administrated to pigs a high-fat and high-cholesterol (HFC) diet for twelve weeks. RNA-Seq was employed to profile renal gene expression in pigs with different testosterone levels. Conclusions: This study demonstrated that testosterone deficiency aggravated renal lipid accumulation in pigs fed an HFC diet and that these effects could be reversed by testosterone replacement therapy. Impaired metabolic processes, bile acid secretion,estrogen signaling pathway and enhanced triglyceride synthesis may contribute to the increased renal lipid accumulation induced by testosterone deficiency and an HFC diet.
2023-01-17 | GSE125343 | GEO
Project description:To gain insight into the role of testosterone in modulating hepatic fat accumulation, we collected liver tissues from high fat diet-fed intact male pigs, castrated male pigs, and castrated male pigs with testosterone replacement. RNA-Seq was employed to profile hepatic gene expression in pigs with different testosterone levels. Liver mRNA profiles of intact male pigs fed a HFC diet, castrated male pigs fed a HFC diet, and castrated male pigs treated with testosterone fed a HFC diet were generated by deep sequencing, using Illumina HiSeq 2000.
2015-01-08 | E-GEOD-62696 | biostudies-arrayexpress
Project description:To gain insight into the role of testosterone in modulating hepatic fat accumulation, we collected liver tissues from high fat diet-fed intact male pigs, castrated male pigs, and castrated male pigs with testosterone replacement. RNA-Seq was employed to profile hepatic gene expression in pigs with different testosterone levels.
2015-01-08 | GSE62696 | GEO
Project description:Testosterone deficiency causes fat deposit, particularly in the visceral region, and its replacement might reverse fat accumulation, but the underlying mechanisms of such processes are largely unclear. To gain insights into the genome-wide role of testosterone on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency induced VAT deposit and increased serum leptin level. Moreover, a total of 1,732 differentially expressed genes (DEGs) were identified between different two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, NCF1 (p47phox), and NOX2 (GP91-PHOX), were mainly enriched in inflammatory response, oxidation-reduction process, and response to oxidative stress, while downregulated genes in CM pigs, i.e., DIO3, PCK1, and ABHD5, mainly focused on small molecule metabolic process. Taken together, our study provides a novel genome-wide view on the role of testosterone on VAT deposit under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency.
2017-02-10 | GSE77544 | GEO
Project description:BackgroundTestosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet.MethodsSexually mature male miniature pigs (6-7 months old) were randomly divided into 3 groups as follows: intact male pigs fed an HFC diet (IM+HFC), castrated male pigs fed an HFC diet (CM+HFC), and castrated pigs with testosterone replacement fed an HFC diet (CM+HFC+T). Serum testosterone levels and lipid profiles were measured, and gene expression levels associated with hepatic cholesterol metabolism were determined. Furthermore, total hepatic cholesterol contents and the activities of enzymes mediating hepatic cholesterol metabolism were measured.ResultsSerum testosterone levels were significantly decreased in CM+HFC pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. Castration significantly increased the serum levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as hepatic lipid contents in pigs fed an HFC diet. Compared with IM+HFC and CM+HFC+T pigs, low-density lipoprotein receptor (LDLR) mRNA expression and protein levels were significantly decreased in the livers of CM+HFC pigs. In contrast, we found that compared with IM+HFC pigs, hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and serum PCSK9 protein levels were significantly increased in CM+HFC pigs. Moreover, testosterone treatment reversed the increase in PCSK9 expression in CM+HFC pigs. However, neither castration nor testosterone replacement affected the expression of the other hepatic genes that were tested.ConclusionsThis study demonstrated that castration-induced testosterone deficiency caused severe hypercholesterolemia in pigs fed an HFC diet; furthermore, these effects could be reversed by testosterone replacement therapy. Altered hepatic PCSK9 and LDLR expression, resulting in reduced LDL-cholesterol clearance, may contribute to the increased serum cholesterol levels induced by testosterone deficiency and an HFC diet. These results deepen our understanding of the underlying molecular mechanisms that mediate the effects of testosterone deficiency on cholesterol metabolism.
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Project description:We used Affymetrix microarrays to investigate gene expression changes in PBMNCs isolated from female and male pigs to determine significant modulatory effects that may have been induced by the intake of resveratrol during 9 months in high-fat fed animals . The aim of this work was to determine whether the intake of dietary levels of resveratrol (RES) exerted any modulatory effects, at the level of gene expression, in PBMNCs isolated from female and male pigs exposed to a H-F diet for 9 months. We first isolated PBMNCs, and the corresponding total RNA, from 5 female pigs and 5 male pigs at time 0 (beginning of the experiment) to determine basal gene expression levels and to compare sex differential gene expression. Animals designated to the control group were then fed a normal chow (5% beef tallow) for 9 months. Animals in the H-F diet were fed a chow with 20% of beef tallow and animals in the H-F diet supplemented with resveratrol were fed the 20% fat diet plus resveratrol (8 mg/Kg body weight per day). From each group, PBMNCs were isolated from 2 female and 2 male animals. Pure RNA was extracted from the PBMNCs for microarrays analyses (Affymetrix) and gene differential expression determined between the H-F fed animals and CT animals (to determine the effects of fat consumption) and between the H-F fed animals supplemented with RES and the H-F group (to determine the effects of RES on the fat consumption).
2010-08-08 | E-GEOD-23503 | biostudies-arrayexpress
Project description:Pharmacological inhibition of megalin (also known as low-density lipoprotein receptor-related protein 2: LRP2) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PTCs), PTC-LRP2 +/+ and -/- littermates in an LDL receptor -/- background were generated and fed a Western diet to determine effects of PTC-derived megalin on atherosclerosis. PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor -/- mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 -/- mice fed the Western diet, but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 -/- mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not hypercholesterolemia. By contrast, female PTC-LRP2 -/- mice had no apparent renal pathologies. In vivo multiphoton microscopy demonstrated that PTC-specific megalin deletion dramatically diminished albumin accumulation in PTCs within 10 days of Western diet feeding. RNA sequencing analyses demonstrated the upregulation of inflammation-related pathways in kidney. Overall, PTC-specific megalin deletion leads to tubulointerstitial nephritis in mice fed Western diet, with severe pathologies in male mice.
2024-07-04 | GSE268879 | GEO
Project description:Fat is an important energy store in animals, especially pigs, because of their high fat deposition ability. In animal husbandry, fat content is closely related to animal's lean meat rate and other important economic traits. Long-chain non-coding RNA regulates numerous biological processes, including lipid metabolism. Resveratrol (RES) has been reported to have anti-obesity effects. However, it is unclear whether RES can control fat deposition in pigs by regulating the activities of long-chain non-coding RNAs (lncRNA). The aim of this study was to examine the expression of lncRNA in subcutaneous fat tissues of pigs fed RES-supplemented diet. A total of 12 Duroc × Landrace × Yorkshire hybrid pigs were randomly assigned to two diets, the control diet and the experimental diet containing 400 mg/kg RES. At the end of the study, RNA sequencing was carried out, and the results indicated the expression of lncRNA in the adipose tissues of pigs from the two groups. A total of 499 lncRNAs were identified. Eighty-two (82) differentially expressed genes, including 5 lncRNAs and 77 mRNAs, were also identified. We also observed that the lncRNAs, MSTRG.12490 and MSTRG.13223 targeted the mRNAs, THBS4 and SFPR2, respectively. Results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes were mainly involved in adipocytokine signaling pathway, Wnt signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway, which are associated with glycolipid metabolism.Results from this study contributes to the knowledge of the genes and pathways involved in fat metabolism in pigs and the role of RES in the diet of pigs.
2022-05-26 | GSE203574 | GEO
Project description:Female Lrp2 (megalin) f/f mice were bred with male Ndrg1-Cre ERT2 +/0 mice to develop PTC-LRP2 +/+ and PTC-LRP2-/- littermates. To study atherosclerosis, all mice were bred to an LDL receptor -/- background and fed a Western diet to induce atherosclerosis. PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor -/- mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 -/- mice fed the Western diet, but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 -/- mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not hypercholesterolemia. In contrast, female PTC-LRP2 -/- mice had no apparent renal pathologies. Urine proteomics analysis discovered that many megalin ligands were increased in urine of male PTC-LRP2 -/- mice, compared to their PTC-LRP2 +/+ littermates.
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Project description:We used Affymetrix microarrays to investigate gene expression changes in PBMNCs isolated from female and male pigs to determine significant modulatory effects that may have been induced by the intake of resveratrol during 9 months in high-fat fed animals .
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