Genes regulated by nuclear Lipin in the fed and fasting state
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA664456 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12668000_1.fastq.gz | Fastqsanger.gz | |||
| SRR12668000_2.fastq.gz | Fastqsanger.gz | |||
| SRR12668001_1.fastq.gz | Fastqsanger.gz | |||
| SRR12668001_2.fastq.gz | Fastqsanger.gz | |||
| SRR12668002_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked how gene expression changes, under both fed and fasting conditions, when nuclear translocation of Lipin is impaired. To address this question, we created a Drosophila mutant expressing Lipin lacking a nuclear localization signal (LipinDNLS). Notably, adult LipinDNLS flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. To examine how these phenotypes correlate with changes in gene expression, we carried out an RNA-seq analysis with mRNA from female and male LipinDNLS and control flies that had been kept under fed or fasting conditions. We found that genes involved in metabolism, feeding behavior, and the immune response were mis-regulated in LipinDNLS flies. The changed expression of these genes supports hypotheses explaining improved life expectancy under fed and decreased life expectancy under fasting conditions. For instance, metabolic rate measurements confirmed the prediction based on the RNA-seq data that energy production by oxidative phosphorylation is reduced in fed LipinDNLS flies.
2020-09-19 | GSE158189 | GEO
Project description:The lipin phosphatidate phosphatase (PAP) enzymes (lipin 1, lipin 2, and lipin 3) catalyze a step in triglyceride and phospholipid biosynthesis, and genetic lipin deficiencies cause human disease that is triggered by metabolic stress, such as fasting. We assessed the protein interactome of lipins 1, 2, and 3 in hepatocytes, and identified unique protein associations between lipin 1 and U2 mRNA spliceosome components. Lpin1–/– mouse liver exhibited aberrant mRNA splicing in the fasted state, including mRNAs involved in mRNA processing and liver maturation. Aberrant splicing could be induced in cultured hepatocytes by lipin 1 knockdown or elevated phosphatidic acid levels, suggesting a role for lipin 1 PAP activity in splicing fidelity. Refeeding Lpin1–/– animals after fasting largely restored mRNA splicing fidelity. Reduced levels of ESRP2 splicing factor exclusively in the fasted state of Lpin1–/– liver was associated with widespread aberrant exon inclusion. These findings connect lipid homeostasis with mRNA splicing, and identify aberrant mRNA splicing in lipin 1 deficiency as a potential contributor to disease symptoms triggered by fasting.
2021-09-15 | GSE160984 | GEO
Project description:Mutations in the gene encoding lipin 1 cause hepatic steatosis in fld mice, a genetic model of lipodystrophy. Lipin 1 appears to be highly involved in the control of fatty acid metabolism. Lipin 1 is most often located in the nucleus, but other studies suggest that lipin also has effects in the cytoplasm. However, the molecular function of lipin 1 is unclear. To evaluate the effects of activation of the lipin 1 system in liver, lipin 1beta was overexpressed in mouse liver using an adenoviral vector. We found that lipin 1 overexpression increased the expression of many genes involved in mitochondrial fatty acid oxidation while repressing expression of genes involved in lipogenesis. We believe that lipin is a transcriptional coactivator of the peroxisome proliferator-activated receptor (PPAR) complex. However, the many molecular aspects of its function remain unclear. Abstract of published manuscript follows: Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway.Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, Lawrence JC Jr, Kelly DP. Center for Cardiovascular Research and Washington University School of Medicine, St. Louis, Missouri 63110; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110. Perturbations in hepatic lipid homeostasis are linked to the development of obesity-related steatohepatitis. Mutations in the gene encoding lipin 1 cause hepatic steatosis in fld mice, a genetic model of lipodystrophy. However, the molecular function of lipin 1 is unclear. Herein, we demonstrate that the expression of lipin 1 is induced by peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha), a transcriptional coactivator controlling several key hepatic metabolic pathways. Gain-of-function and loss-of-function strategies demonstrated that lipin selectively activates a subset of PGC-1alpha target pathways, including fatty acid oxidation and mitochondrial oxidative phosphorylation, while suppressing the lipogenic program and lowering circulating lipid levels. Lipin activates mitochondrial fatty acid oxidative metabolism by inducing expression of the nuclear receptor PPARalpha, a known PGC-1alpha target, and via direct physical interactions with PPARalpha and PGC-1alpha. These results identify lipin 1 as a selective physiological amplifier of the PGC-1alpha/PPARalpha-mediated control of hepatic lipid metabolism. Keywords: response to lipin 1 activation
2006-08-16 | GSE5538 | GEO
Project description:Mutations in the gene encoding lipin 1 cause hepatic steatosis in fld mice, a genetic model of lipodystrophy. Lipin 1 appears to be highly involved in the control of fatty acid metabolism. Lipin 1 is most often located in the nucleus, but other studies suggest that lipin also has effects in the cytoplasm. However, the molecular function of lipin 1 is unclear. To evaluate the effects of activation of the lipin 1 system in liver, lipin 1beta was overexpressed in mouse liver using an adenoviral vector. We found that lipin 1 overexpression increased the expression of many genes involved in mitochondrial fatty acid oxidation while repressing expression of genes involved in lipogenesis. We believe that lipin is a transcriptional coactivator of the peroxisome proliferator-activated receptor (PPAR) complex. However, the many molecular aspects of its function remain unclear. Abstract of published manuscript follows:; Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway.Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, Lawrence JC Jr, Kelly DP. Center for Cardiovascular Research and Washington University School of Medicine, St. Louis, Missouri 63110; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110. Perturbations in hepatic lipid homeostasis are linked to the development of obesity-related steatohepatitis. Mutations in the gene encoding lipin 1 cause hepatic steatosis in fld mice, a genetic model of lipodystrophy. However, the molecular function of lipin 1 is unclear. Herein, we demonstrate that the expression of lipin 1 is induced by peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha), a transcriptional coactivator controlling several key hepatic metabolic pathways. Gain-of-function and loss-of-function strategies demonstrated that lipin selectively activates a subset of PGC-1alpha target pathways, including fatty acid oxidation and mitochondrial oxidative phosphorylation, while suppressing the lipogenic program and lowering circulating lipid levels. Lipin activates mitochondrial fatty acid oxidative metabolism by inducing expression of the nuclear receptor PPARalpha, a known PGC-1alpha target, and via direct physical interactions with PPARalpha and PGC-1alpha. These results identify lipin 1 as a selective physiological amplifier of the PGC-1alpha/PPARalpha-mediated control of hepatic lipid metabolism. Experiment Overall Design: Adult male C57BL6 mice were injected with adenovirus driving expression of mouse lipin 1beta or green fluorescent protein (GFP). Mice were recovered and sacrificed 6 days after injection. Total RNA was isolated and analyzed using Affymetrix microarray.
2008-06-13 | E-GEOD-5538 | biostudies-arrayexpress
Project description:Lipin 1 regulates mRNA splicing in fasting and feeding in mouse liver
| PRJNA675070 | ENA
Project description:We report the RNA sequencing results of four fasting mice with humanized livers and four fed mice with humanized livers.
2019-10-04 | GSE126587 | GEO
Project description:The lipin family consists of three members (lipin-1, lipin-2 and lipin-3) that are phosphatidate phosphatases. Lipins facilitate lipid synthesis and remodeling through the conversion of phosphatidic acid to diacylglycerol. Lipin-1 and lipin-2 are also transcriptional co-regulators of peroxisome proliferator-activated receptors (PPARs). Our previous studies showed differential lipin-1 expression in numerous prostate cancer cell lines, and the lipin-1 expression was higher in cells representing advanced prostate cancer. However, the role of lipin-1 in prostate cancer cell growth is not fully understood. This study addressed the role of lipin-1 in prostate cancer cell function by performing RNA sequencing and qualitative LC-MS/MS analysis in PC-3 cells in which the gene for lipin-1 (LPIN1) was genetically inhibited. Transcriptomic and lipidomic analyses of LPIN1 knockdown PC-3 cells demonstrated alterations in the expression of numerous genes and the peak intensities of several lipids. The genes and lipids aligned with pathways that mediate focal adhesion, glycerophospholipid metabolism (GM), and PPAR signaling. Additionally, treatment of PC-3 cells with curcumin, a suggested inhibitor of lipin, decreased lipin-1 and lipin-3 expression, with no effect on lipin-2 expression. Bioinformatic analysis of prostate cancer patients demonstrated a correlation between LPIN3 mRNA expression and higher Gleason scores (8-10). These data show the novel findings that lipin-1 mediates the lipidome of castration-resistant prostate cancer cells and identified several pathways that it regulates, beyond GM and PPAR. Additionally, these data suggest that curcumin may be used to treat advanced prostate cancer that overexpresses lipin-3.
2023-11-17 | GSE247919 | GEO
Project description:Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing Lipin lacking a nuclear localization signal (LipinΔNLS ), and a mutant expressing enzymatically dead Lipin. Our data support the conclusion that the enzymatic but not nuclear gene regulatory activity of Lipin is essential for survival. Notably, adult LipinΔNLS flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. Both the improved life expectancy in the fed state and the decreased survival in the fasting state correlated with changes in metabolic gene expression. Moreover, increased life expectancy of fed flies was associated with a decreased metabolic rate. Interestingly, in addition to metabolic genes, genes involved in feeding behavior and the immune response were misregulated in LipinΔNLS flies. Altogether, our data suggest that the nuclear activity of Lipin influences the genomic response to nutrient availability with effects on life expectancy and starvation resistance. Thus, nutritional or therapeutic approaches that aim at lowering nuclear translocation of lipins in humans may be worth exploring.
| S-EPMC7707171 | biostudies-literature
Project description:Lipin-1 affects the expression levels of many genes during TLR4 stimulation of macrophages. Gene expression analysis of peritoneal macrophages from four control (hetorozygotes) mice and four lipin-1 mutant (fatty liver distrophy, fld) mice stimulated with 100 ng/ml LPS for 5 hours.
2014-10-01 | E-GEOD-54155 | biostudies-arrayexpress
Project description:Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Two independent replicates were performed. Total RNA was extracted with TRIzol (Invitrogen). The extracted RNA was purified with PureLink RNA Micro Kit (Invitrogen) and analyzed with Agilent 2100 Bioanalyzer to assess the RNA integrity. The microarray procedures were performed according to Affymetrix protocols. Hybridized arrays were scanned using an Affymetrix GeneChip Scanner.
2017-05-01 | E-GEOD-51046 | biostudies-arrayexpress