Correction to: Transcriptomic analysis of hepatic responses to testosterone deficiency in miniature pigs fed a high-cholesterol diet.
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ABSTRACT:
SUBMITTER: Cai Z
PROVIDER: S-EPMC6964042 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Correction to: Transcriptomic analysis of hepatic responses to testosterone deficiency in miniature pigs fed a high-cholesterol diet.
Cai Zhaowei Z Jiang Xiaoling X Pan Yongming Y Chen Liang L Zhang Lifan L Zhu Keyan K Cai Yueqin Y Ling Yun Y Chen Fangming F Xu Xiaoping X Chen Minli M
BMC genomics 20200116 1
Following the publication of the original article [1], it was reported that the accession number given in the 'Data accessibility' declaration, GSE65696, is incorrect. ...[more]
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Project description:BackgroundRecent studies have indicated that low serum testosterone levels are associated with increased risk of developing hepatic steatosis; however, the mechanisms mediating this phenomenon have not been fully elucidated. To gain insight into the role of testosterone in modulating hepatic steatosis, we investigated the effects of testosterone on the development of hepatic steatosis in pigs fed a high-fat and high-cholesterol (HFC) diet and profiled hepatic gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT).ResultsSerum testosterone levels were significantly decreased in CM pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. CM pigs showed increased liver injury accompanied by increased hepatocellular steatosis, inflammation, and elevated serum alanine aminotransferase levels compared with IM pigs. Moreover, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were markedly increased in CM pigs. Testosterone replacement decreased serum and hepatic lipid levels and improved liver injury in CM pigs. Compared to IM and CMT pigs, CM pigs had lower serum levels of superoxide dismutase but higher levels of malondialdehyde. Gene expression analysis revealed that upregulated genes in the livers of CM pigs were mainly enriched for genes mediating immune and inflammatory responses, oxidative stress, and apoptosis. Surprisingly, the downregulated genes mainly included those that regulate metabolism-related processes, including fatty acid oxidation, steroid biosynthesis, cholesterol and bile acid metabolism, and glucose metabolism. KEGG analysis showed that metabolic pathways, fatty acid degradation, pyruvate metabolism, the tricarboxylic acid cycle, and the nuclear factor-kappaB signaling pathway were the major pathways altered in CM pigs.ConclusionsThis study demonstrated that testosterone deficiency aggravated hypercholesterolemia and hepatic steatosis in pigs fed an HFC diet and that these effects could be reversed by testosterone replacement therapy. Impaired metabolic processes, enhanced immune and inflammatory responses, oxidative stress, and apoptosis may contribute to the increased hepatic steatosis induced by testosterone deficiency and an HFC diet. These results deepened our understanding of the molecular mechanisms of testosterone deficiency-induced hepatic steatosis and provided a foundation for future investigations.
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Project description:Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen 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 significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, S100A9, NCF1 (p47phox), and LEP, were mainly involved in inflammatory response, oxidation-reduction process, and lipid metabolic process, while downregulated genes in CM pigs, i.e., ABHD5, SPP1, and GAS6, were focused on cell differentiation and cell adhesion. Taken together, our study demonstrates that testosterone deficiency alters the expression of numerous genes involved in key biological processes of VAT accumulation under HFC diet and provides a novel genome-wide view on the role of androgen on VAT deposition under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency.
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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: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: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: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:Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of familial hypercholesterolemia and atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 system (CRISPR/Cas9) was used to disrupt the ApoE gene in Bama miniature pigs. Biallelic-modified ApoE pigs with in-frame mutations (ApoEm/m ) and frameshift mutations (ApoE-/- ) were simultaneously produced. ApoE-/- pigs exhibited moderately increased plasma cholesterol levels when fed with a regular chow diet, but displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries after feeding on a high-fat and high-cholesterol (HFHC) diet for 6 months. Thus, these ApoE-/- pigs could be valuable large animal models for providing further insight into translational studies of atherosclerosis.
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