Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174693 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Angiopoietin-like protein 4 (ANGPTL4, also referred to as Fiaf) has been proposed as a circulating mediator between the gut microbiota and fat storage in adipose tissue. Very little is known about the mechanisms of regulation of ANGPTL4 in the colon. Here we show that transcription and subsequent secretion of ANGPTL4 in human T84 and HT-29 colonocytes is highly induced by physiological concentrations of products of bacterial fermentation, the short-chain fatty acids. Short-chain fatty acids induce ANGPTL4 by activating the nuclear receptor PPARγ, as shown by microarray, transactivation assays, coactivator peptide recruitment assay, and use of PPARγ antagonist. At concentrations required for PPARγ activation and ANGPTL4 induction in colonocytes, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modelling. It can be concluded that 1) SCFA potently stimulate ANGPTL4 synthesis in human colonocytes, and 2) SCFA transactivate and bind to PPARγ by serving as selective PPAR modulators. Our data point to activation of PPARγ as a novel mechanism of gene regulation by SCFA in the colon.
2013-03-11 | GSE40706 | GEO
Project description:Angiopoietin-like protein 4 (ANGPTL4, also referred to as Fiaf) has been proposed as circulating mediator between the gut microbiota and fat storage in adipose tissue. Very little is known about mechanisms of regulation of ANGPTL4 in the colon. Here we show that transcription and subsequent secretion of ANGPTL4 in human T84 and HT-29 colonocytes is highly induced by physiological concentrations of products of bacterial fermentation, the short chain fatty acids (SCFA). Induction of ANGPTL4 by SCFA cannot be mimicked by the histone deacetylase inhibitor Trichostatin A. SCFA induce ANGPTL4 by activating the nuclear receptor PPARγ, as shown by use of PPARγ antagonist, PPARγ knock-down, and transactivation assay, which shows activation of PPARγ but not PPARα and PPARδ. At concentrations required for PPARγ activation and ANGPTL4 induction in colonocytes, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modelling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin was associated with induction of PPAR target genes and pathways in the colon, as shown by microarray and subsequent gene set enrichment analysis. It can be concluded that 1) SCFA potently stimulate ANGPTL4 synthesis in human colonocytes; 2) SCFA transactivate and bind to PPARγ by serving as selective PPAR modulators. Our data point to activation of PPARγ as a novel mechanism of gene regulation by SCFA in the colon.
2013-03-11 | GSE43065 | GEO
Project description:Short chain fatty acids induce ANGPTL4 via PPARγ
| PRJNA184303 | ENA
Project description:Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects. Twenty-one microarrays: three diets (CO, FO, KO) x seven mice per diet x one microarray per mouse
2011-07-21 | E-GEOD-29572 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to find out the differential expression genes in the fadR mutant strain(ΔfadR) compared with wild-type (WT) and to further explore the regulation mechanisms of fadR. Methods: Shewanella oneidensis MR-1 WT and ΔfadR were collected in log phage(OD~0.6). RNA extraction was performed using the RNeasy minikit (Qiagen) and the RNA was quantified by using a NanoVue spectrophotometer (GE Healthcare). RNA seq was performed using Illumina NextSeq 500, 2×150 bp. Results: Our study represents that the expression of 146 genes were decreased and 94 genes were increased inΔfadR compared with WT. Branched-chain keto acid dehydrogenase (BKD) produces corresponding branched-chain acyl coenzyme A which further participating branchend-chain fatty acids synthesis. The expression of bkdA2 was also promoted in △fadR compared with WT. Conclusions: Combined with our expression results, it declared that FadR can suppress bkd operon in some degree,which further increase the synthesis of branched-chain fatty acids in ΔfadR.
2020-01-01 | GSE133375 | GEO
Project description:Medium chain fatty acid (MCFAs) synthesis Metagenome
| PRJNA950190 | ENA
Project description:When macrophages are activated by sensing bacterial lipopolysaccharides (LPS), they greatly increase their motility, mRNA synthesis and protein production. Most of the ATP needed for these responses is derived from the uptake and catabolism of glucose, a relatively inefficient ATP source. Although the stimulated cells also increase their uptake of free fatty acids, they store a large fraction as triglycerides (TAG). We report here that both Toll-like receptor 4 (TLR4) and TLR2 agonists stimulate prolonged TAG retention by primary murine and human macrophages. Agonist-induced TAG storage lasted at least 72-96 hrs in vitro and was associated with increases in fatty acid (FA) uptake, FA esterification, and FA incorporation into TAG; FA oxidation decreased. The results of expression and inhibitor studies support a prominent role for increases in long chain acyl CoA synthase 1 (ACSL1) and diacylglycerol acyltransferase-2 (DGAT2) during the sustained response to TLR2/4 activation; decreases in adipose triglyceride lipase (ATGL, Pnpla2) and monoacylglycerol lipase (MgII) may also contribute. Stimulated murine macrophages that retained TAG carried out phagocytosis more effectively and were protected from saturated fatty acid-induced cell death (lipotoxicity). TLR agonist-induced TAG retention in macrophages is thus an active, sustained process that may have important adaptive functions. It may also contribute to the persistence of lipid-laden macrophages in infected tissues, host susceptibility to some microbial pathogens, and the pathogenesis of atherosclerosis. RNA from macrophage loaded with Fatty Acids, stimulated with bacterial lipopolysaccharides (LPS), or both compared to untreated controls (FA, LPS, FA+LPS, untreated). Replicates from 4 independent experiments.
2013-12-17 | E-GEOD-42190 | biostudies-arrayexpress
Project description:The de novo synthesis of fatty acids has emerged as a therapeutic target for various diseases including cancer. Since cancer cells are intrinsically buffered to combat metabolic stress, it is important to understand how cells may adapt to loss of de novo fatty acid biosynthesis. Here we use pooled genome-wide CRISPR screens to systematically map genetic interactions (GIs) in human HAP1 cells carrying a loss-of-function mutation in FASN, which catalyzes the formation of long-chain fatty acids. FASN mutant cells show a strong dependence on lipid uptake that is reflected by negative GIs with genes involved in the LDL receptor pathway, vesicle trafficking, and protein glycosylation. Further support for these functional relationships is derived from additional GI screens in query cell lines deficient for other genes involved in lipid metabolism, including LDLR, SREBF1, SREBF2, ACACA. Our GI profiles also identify a potential role for the previously uncharacterized gene LUR1/C12orf49 in exogenous lipid uptake regulation through modulation of SREBF2 signalling in response to lipid starvation. Overall, our data highlight the genetic determinants underlying the cellular adaptation associated with loss of de novo fatty acid synthesis and demonstrate the power of systematic GI mapping for uncovering metabolic buffering mechanisms in human cells.
2020-04-30 | GSE148627 | GEO
Project description:The de novo synthesis of fatty acids has emerged as a therapeutic target for various diseases including cancer. Since cancer cells are intrinsically buffered to combat metabolic stress, it is important to understand how cells may adapt to loss of de novo fatty acid biosynthesis. Here we use pooled genome-wide CRISPR screens to systematically map genetic interactions (GIs) in human HAP1 cells carrying a loss-of-function mutation in FASN, which catalyzes the formation of long-chain fatty acids. FASN mutant cells show a strong dependence on lipid uptake that is reflected by negative GIs with genes involved in the LDL receptor pathway, vesicle trafficking, and protein glycosylation. Further support for these functional relationships is derived from additional GI screens in query cell lines deficient for other genes involved in lipid metabolism, including LDLR, SREBF1, SREBF2, ACACA. Our GI profiles also identify a potential role for the previously uncharacterized gene LUR1/C12orf49 in exogenous lipid uptake regulation through modulation of SREBF2 signalling in response to lipid starvation. Overall, our data highlight the genetic determinants underlying the cellular adaptation associated with loss of de novo fatty acid synthesis and demonstrate the power of systematic GI mapping for uncovering metabolic buffering mechanisms in human cells.
2020-04-30 | GSE147770 | GEO