MiR-29 regulates de novo lipogenesis and controls circulating triglyceride levels in a Sirt1-dependent manner
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA531687 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8870790.fastq.gz | Fastqsanger.gz | |||
| SRR8870800.fastq.gz | Fastqsanger.gz | |||
| SRR8870810.fastq.gz | Fastqsanger.gz | |||
| SRR8870820.fastq.gz | Fastqsanger.gz | |||
| SRR8870791.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 37 |
Similar Datasets
Project description:MiR-29 Regulates de novo Lipogenesis in the Liver and Circulating Triglyceride Levels in a Sirt1-Dependent Manner
| PRJNA503253 | ENA
Project description:Investigation of the effect of miR-29 on de novo lipogenesis.
2019-08-09 | GSE129539 | GEO
Project description:MicroRNAs (miRNAs) are known regulators of lipid homeostasis. We recently demonstrated that miR-29 controls the levels of circulating cholesterol and triglycerides, but the mechanisms remained unknown. In the present study, we demonstrated that systemic delivery of locked nucleic acid inhibitor of miR-29 (LNA29) through subcutaneous injection effectively suppresses hepatic expression of miR-29 and dampens de novo lipogenesis (DNL) in the liver of chow-fed mice. Next, we used mice with liver-specific deletion of Sirtuin 1 (L-Sirt1 KO), a validated target of miR-29, and demonstrated that the LNA29-induced reduction of circulating triglycerides, but not cholesterol, is dependent on hepatic Sirt1. Moreover, lipidomics analysis revealed that LNA29 suppresses hepatic triglyceride levels in a liver-Sirt1 dependent manner. A comparative transcriptomic study of liver tissue from LNA29-treated wild-type/floxed and L-Sirt1 KO mice identified the top candidate lipogenic genes and hepatokines through which LNA29 may confer its effects on triglyceride levels. The transcriptomic analysis also showed that fatty acid oxidation (FAO) genes respond differently to LNA29 depending on the presence of hepatic Sirt1. Overall, this study demonstrates the beneficial effects of LNA29 on DNL and circulating lipid levels. In addition, it provides mechanistic insight that decouples the effect of LNA29 on circulating triglycerides from that of circulating cholesterol.
| S-EPMC6828850 | biostudies-literature
Project description:Systematic comparison of multiple models of diabetes / insulin resistance reveals miR-29 as a commonality among them, and further analysis reveals it as a key therapeutic target for insulin resistance.
2019-10-29 | GSE122044 | GEO
Project description:Fate and behaviour of neural progenitor cells is tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells, govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multi-enzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors (APs) and reduced progenitor proliferation. Further, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell (ESC)-derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity and progenitor expansion in the developing human forebrain. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor cell polarity and lipid metabolism.
2022-01-14 | PXD026110 | Pride
Project description:Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption.
| S-EPMC3770099 | biostudies-literature
Project description:Insulin integrates hepatic glucose and lipid metabolism, directing nutrients to storage as glycogen and triglyceride. In type 2 diabetes, levels of the former are low and the latter are exaggerated, posing a pathophysiologic and therapeutic conundrum. A branching model1 of insulin signaling, with FoxO1 presiding over glucose production2-5 and Srebp–1c regulating lipogenesis,6-8 provides a potential explanation. Here we illustrate an alternative mechanism that integrates glucose production and lipogenesis under the unifying control of FoxO. Liver–specific ablation of three FoxOs (L–FoxO1,3,4) prevents the induction of glucose–6–phosphatase and the repression of glucokinase during fasting, thus increasing lipogenesis at the expense of glucose production. We document a similar pattern in the early phases of diet-induced insulin resistance, and propose that FoxOs are required to enable the liver to direct nutritionally derived carbons to glucose vs. lipid metabolism. Our data underscore the heterogeneity of hepatic insulin resistance during progression from the metabolic syndrome to overt diabetes, and the conceptual challenge of designing therapies that curtail glucose production without promoting hepatic lipid accumulation. We used microarrays to detail the change of gene expression in liver after knocking out FoxO1,3 and 4. Liver tissue samples were collected from hepatocyte- specific triple FoxO(1,3, and 4) KO and their littermates control (WT) mice after fasting (22 h) or refeeding (4 h). Gene expression was analyzed by microarray. Mice were on a mixed background of C57BL/6J and 129.
2014-08-20 | E-GEOD-60527 | biostudies-arrayexpress
Project description:Cystic fibrosis (CF) mouse models exhibit exocrine pancreatic function yet do not develop adipose stores to the levels of non-CF mice. CF mice homozygous for the Cftr mutation (F508del) at 3 weeks (post-weaning) and 6 weeks (young adult) of age had markedly less adipose tissue than non-CF mice. Both 3- and 6-week old mice had dietary lipid absorption and fecal lipid excretion comparable to non-CF controls. Fractional hepatic de novo synthesis of palmitate and stearate (de novo lipogenesis, DNL) as determined by deuterium incorporation was reduced in CF mice. At 3 weeks of age, F508del mice had significantly decreased DNL of palmitate and stearate, by 83% and 80%, respectively. By 6 weeks of age, DNL rates in non-CF mice remained unchanged as compared to 3-week old mice, while DNL rates of F508del mice were still reduced, by 33% and 40%, respectively. Adipose tissue fatty acid profiles were comparable in CF and non-CF mice, indicating that adipose differences are quantitative, not qualitative. A correspondingly lower content of deuterium-labeled fatty acids was found in CF adipose tissue, consistent with reduced deposition of newly made hepatic triglycerides and/or decreased adipose tissue lipogenesis. Hepatic transcriptome analysis revealed lower mRNA expression from several genes involved in fatty acid biosynthesis, suggesting down-regulation of several enzymes in fatty acids synthesis as a mechanism for the reduced lipogenesis. These novel data provide a model for altered fat and fatty acid metabolism in CF, independent of malabsorption, and may partly explain the inability of pancreatic enzyme replacement therapy to completely restore normal body mass to CF patients ∆F508 CF mice and its WT littermates (3-weeks old females, C57BL/6J) were examined. RNA extracted from snapped-frozen livers, 4 replicates per genotype.
2012-06-17 | E-GEOD-33319 | biostudies-arrayexpress
Project description:Sirtuin-1 (Sirt1), a class III histone/protein deacetylase is central to cellular metabolism, stress responses and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T-cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression and acetylation of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4+ T-cells or Foxp3+ Treg cells exhibited prolonged survival of MHC-mismatched cardiac allografts. Allografts in Sirt1 targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3+ Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions and its targeting may have therapeutic value in autoimmunity and transplantation.
2011-01-05 | GSE26425 | GEO
Project description:Sirtuin-1 (Sirt1), a class III histone/protein deacetylase is central to cellular metabolism, stress responses and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T-cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression and acetylation of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4+ T-cells or Foxp3+ Treg cells exhibited prolonged survival of MHC-mismatched cardiac allografts. Allografts in Sirt1 targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3+ Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions and its targeting may have therapeutic value in autoimmunity and transplantation. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of Sirt1 knock out, compared to wild type (C57BL6) control
2011-01-05 | E-GEOD-26425 | biostudies-arrayexpress