Acinetobacter baumannii Fatty Acid Desaturases Facilitate Survival in Distinct Environments
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ABSTRACT:
PROVIDER: PRJNA684913 | ENA |
REPOSITORIES: ENA
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Project description:RNA sequencing transcriptomics was performed on a highly multidrug resistant A. baumannii strain belonging to international clone I, AB5075_UW and a transposon insertion inactivated mutant of ABUW_1103 (DesT1), which encodes for a TetR family regulator. Transcriptomics revealed that DesT1 might function as a global regulator controlling expression of various genes involved in fatty acid metabolism and transport and a range of outer membrane proteins. Genes encoding acyl-CoA desaturase and ferredoxin reductase were found to be significantly upregulated when DesT1 regulator was inactivated. Aerobic desaturases are known to play an important role in maintaining membrane homeostasis.
2021-06-15 | GSE163107 | GEO
Project description:Free fatty acids accumulate in tumor microenvironment which facilitate the polarization of bone marrow derived myeloid cells into tumor associated macrophages. However, the underlying mechanism is still unclear. Here we use microarray to detail the impact of variant free fatty acids on the maturation of bone marrow derived myeloid cells.
2018-08-04 | GSE118080 | GEO
Project description:Maternal obesity and gestational diabetes mellitus (GDM) are associated with adverse intrauterine environments that are high in circulating nutrients. These adverse environments facilitate impairments in placental mitochondrial function and nutrient processing that ultimately leads to an increased risk of the exposed offspring developing non-communicable cardiometabolic health disorders (e.g. obesity, type 2 diabetes, metabolic syndrome). Analysis of fasting serum lipid levels in the third trimester has highlighted that Palmitate (PA) and oleate (OA) are the most abundance non-esterified fatty acids (NEFAs) in circulation. More importantly, these important NEFAs are elevated in both obese and GDM pregnancies. As PA and OA are the most abundant NEFAs in the typical “Westernized Diet” they elevated levels in obese and GDM pregnancies may highlight increased maternal consumption of these fats and could be a link between poor diet and abberant placental function. However, the independent and combined impacts of dietary PA and OA on mitochondrial function and nutrient processing in placental trophoblast cells remains poorly defined. Thus, in this study we sought to utilize a multi-omics approach (combining transcriptomics with untargeted metabolomics and lipidomics) to elucidate the underlying impacts of elevated NEFA levels on BeWo placental trophoblast cells. We highlighted a significant enrichment in the Wikipathways Fatty Acid Biosynthesis Pathway in BeWo cytotrophoblast cells treated with a combination of PA and OA (P/O; 50 µM each). Further, we identified differential expression of genes involved in lipid processing (e.g. ACADVL, ACACB, ACSL5, CREB3L3, PLIN2, and SCD) in BeWo cytotrophoblast cells treated with dietary NEFA species. Overall, these data highlighted that alterations in lipid processing, storage, and oxidation are implicated in the development of placental dysfunction in response to elevated lipid levels.
2023-08-30 | GSE197385 | GEO
Project description:Free fatty acids play an important role during infection by modulating immune responses, but also by directly functioning as antimicrobials. Particularly, the host’s long chain polyunsaturated fatty acids, not commonly found in bacterial pathogens, have significant antibacterial potential. Of these arachidonic acid (AA) is in high abundance, and in this study we show that upon infection with the Streptococcus pneumoniae the AA concentration in the blood increases. Hence, we investigated the transcriptmoic effects of AA on this extremely problematic bacterial pathogen.
2018-05-23 | GSE93102 | GEO
Project description:Metabolic diseases are closely linked to aberrant synthesis of endogenous fatty acids in the liver, called de novo lipogenesis (DNL), which is mediated by the enzyme fatty acid synthase (FASN). The composition of complex lipids consists of saturated or monosaturated fatty acids, which can be endogenously produced, and polyunsaturated fatty acids (PUFA), which are strictly dietary. Compositional differences between individuals are insufficiently understood and may influence the onset and progression of metabolic and cardiovascular diseases. Here we show that DNL critically determines the use of dietary PUFA. A patient with a hypofunctional heterozygous de novo Arg2177Cys variant in FASN exhibited an elevated composition of PUFA, which was phenocopied by pharmacological inhibition of FASN with TVB-2640 in patients with nonalcoholic steatohepatitis (NASH). In mice, the incorporation rate of supplemented omega-3 PUFA during an obesogenic diet was increased by genetic or pharmacologic reduction of DNL. Mechanistically, we show that the FASN variant exhibited a cysteine-dependent, non-enzymatic acetylation of FASN, which resulted in hyperubiquitinylation and decreased protein stability. Our study further reveals that PUFA storage is an active, enzymatic process controlled by FASN, diacylglycerol O-acyltransferase 2 (DGAT2) and MFSD2A, a membrane-transport protein, and that combining FASN inhibition and PUFA supplementation exerts additive beneficial metabolic effects. These findings provide evidence that the success of PUFA supplementation may depend on the rate of endogenous DNL and that combined PUFA supplementation and FASN inhibition may be a promising approach targeting metabolic disease.
2023-12-19 | PXD045908 | Pride
Project description:Survival of the foodborne pathogen Listeria monocytogenes in acidic environments (e.g., stomach and low pH foods) is vital to its transmission. L. monocytogenes grows at temperatures as low as 2°C, and refrigerated, ready-to-eat foods have been sources of L. monocytogenes outbreaks. The purpose of this study was to determine whether growth at a low temperature (i.e., 7°C) affects the response of L. monocytogenes to sudden acid shock.
2011-07-01 | GSE22672 | GEO
Project description:Background: More than 90% mortality of triple negative breast cancer (TNBC) patients are attributed to cancer metastasis with organotropism. Lung is the frequent site of TNBC metastasis. However, the precise mechanism of lung-specific metastasis of TNBC, particularly the driving factors, is not well understood. Methods: RNA sequencing was performed to identify patterns of gene expression associated with lung metastatic behavior using 4T1-LM3, 231-LM3 and their parental cells (4T1-P, 231-P). Expressions of RGCC, encoding the completion 32 protein response protein, were detected in TNBC cells and tissues by qRT-PCR, western blotting and IHC. Kinase activity assay were performed to evaluated PLK1 kinase activity and the amount of phosphorylated AMP-activated protein kinase α2 (AMPKα2). RGCC-mediated metabolism was determined by UHPLC system. Oxidative phosphorylation was evaluated by JC-1 staining and oxygen consumption rate (OCR) assay. Fatty acid oxidation assay, NADPH and ROS was applied to measure the status of RGCC-mediated fatty acid oxidation. The chemical sensitivity of cells was evaluated by CCK8 assay. Results: RGCC is aberrantly upregulated in pulmonary metastatic cells. High level of RGCC is significantly related with lung metastasis rather than other organ metastases. RGCC can effectively promote the kinase activity of PLK1, and activated PLK1 phosphorylates AMPKα2 to facilitate TNBC lung metastasis. Mechanistically, Survival and colonization of TNBC cells in the lungs by upregulating oxidative phosphorylation of mitochondria to obtain more energy and promoting fatty acid oxidation to produce abundant NADPH and sustains redox homeostasis, thus prevents excessive accumulation of potentially detrimental ROS in metastatic tumor cells, ultimately establishing metastases. Importantly, targeting RGCC in combination with paclitaxel/carboplatin effectively suppresses pulmonary metastases of TNBC in a mouse model. Conclusions: The enhanced RGCC is closely associated with lung-specific metastasis of TNBC. RGCC leads to activation of AMPKα2 and downstream signaling through RGCC-driven PLK1 activity to facilitate TNBC lung metastasis, which may determine a potential value of RGCC-driven OXPHOS and fatty acid oxidation as an important therapeutic target.
2023-11-01 | GSE246749 | GEO
Project description:Estrogen receptor dependent genomic expression profiles in breast cancer cells in response to fatty acids. Estrogen receptor positive cells respond better to omega 3 treatments. two condition experiments: ER positive and negative breast cancer cells exposed to two fatty acids: omega-3 (eicosapentanoic acid) and 6 (arachidonic acid).
2010-05-22 | E-GEOD-14679 | biostudies-arrayexpress
Project description:The current study was designed to determine if dietary fatty acid concentration and composition affects the development and progression of nonalcoholic fatty liver disease. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated), or corn oil (polyunsaturated). Overfeeding 5% corn oil produced little steatosis relative to feeding 5% olive oil. This was associated with lower fatty acid synthesis and reduced SREBP-c signaling in the 5% corn oil group. Overfeeding 70% fat diets increased steatosis and lead to increased liver necrosis in the 70% corn oil but not olive oil group. Increased injury after feeding polyunsaturated fat diets was linked to peroxidizability of hepatic free fatty acids and triglycerides and appearance of peroxidaized lipid products HETES and HODES previously linked to clinical nonalcoholic steatohepatitis. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated) or corn oil (polyunsaturated).
2011-10-23 | E-GEOD-33166 | biostudies-arrayexpress
Project description:Organelle interactions play a significant role in compartmentalizing metabolism and signaling. Lipid droplets (LDs) interact with numerous organelles including mitochondria, which is largely assumed to facilitate lipid transfer and catabolism. However, quantitative proteomics of hepatic peridroplet (PDM) and cytosolic mitochondria (CM) revealed that CM are enriched in proteins comprising various oxidative metabolism pathways whereas PDM are enriched in proteins involved in lipid anabolism. Isotope tracing and super-resolution imaging confirmed that fatty acids (FAs) are selectively trafficked to and oxidized in CM during fasting. In contrast, PDM facilitate FA esterification and LD expansion in nutrient-replete media. Additionally, mitochondrial-associated membranes (MAMs) around PDM and CM differed in their proteomes and ability to support distinct lipid metabolic pathways. We conclude that CM and CM-MAM support lipid catabolic pathways whereas PDM and PDM-MAM allow hepatocytes to efficiently store excess lipids in LDs to prevent lipotoxicity in contrast to existing dogma.
2023-03-28 | MSV000091575 | MassIVE