Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-58358
PROVIDER: PRJNA252430 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Severe infections and sepsis is an increasing clinical problem that cause prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of antibiotic resistance is increasing and it is therefore critical to find new therapies for sepsis. Staphylococcus aureus (S. aureus) is a major cause of septic mortality. Neutrophils play a major role in defense against bacterial infections. We have recently shown that a saturated high fat diet decreases survival in septic mice, but the mechanisms behind remain elusive. The aim of the present study was to investigate how the dietary fat composition affects survival and neutrophils function after experimental septic infection in mice. We found that, after S. aureus infection, mice fed polyunsaturated high fat diet (HFD/P) for 8 weeks had increased septic survival and decreased bacterial load compared with mice fed saturated HFD (HFD/S), and similar to that of mice given low fat diet (LFD). Furthermore, uninfected mice fed HFD/P had increased number of Ly6G+ neutrophils in bone marrow. In addition, mice fed HFD/P had a higher number Ly6G+ neutrophils recruited to the site of inflammation after peritoneal injection of thioglycollate. In conclusion, polyunsaturated dietary fat increased both survival and the efficiency of the bacterial clearance during septic S. aureus infection. Moreover, this diet enhanced the number and chemotaxis of neutrophils, a key component of the immune response to S. aureus infections. Mice (non-infected) fed saturated high fat diet, low fat diet, or polyunsaturated high fat diet
2014-11-24 | E-GEOD-58358 | biostudies-arrayexpress
Project description:Severe infections and sepsis is an increasing clinical problem that cause prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of antibiotic resistance is increasing and it is therefore critical to find new therapies for sepsis. Staphylococcus aureus (S. aureus) is a major cause of septic mortality. Neutrophils play a major role in defense against bacterial infections. We have recently shown that a saturated high fat diet decreases survival in septic mice, but the mechanisms behind remain elusive. The aim of the present study was to investigate how the dietary fat composition affects survival and neutrophils function after experimental septic infection in mice. We found that, after S. aureus infection, mice fed polyunsaturated high fat diet (HFD/P) for 8 weeks had increased septic survival and decreased bacterial load compared with mice fed saturated HFD (HFD/S), and similar to that of mice given low fat diet (LFD). Furthermore, uninfected mice fed HFD/P had increased number of Ly6G+ neutrophils in bone marrow. In addition, mice fed HFD/P had a higher number Ly6G+ neutrophils recruited to the site of inflammation after peritoneal injection of thioglycollate. In conclusion, polyunsaturated dietary fat increased both survival and the efficiency of the bacterial clearance during septic S. aureus infection. Moreover, this diet enhanced the number and chemotaxis of neutrophils, a key component of the immune response to S. aureus infections.
2014-11-24 | GSE58358 | GEO
Project description:Abstract Cardiovascular disease (CVD) is closely associated with obesity through risk factors such as dyslipidemia and chronic low-grade inflammation, which may be affected by diet. Dietary fats have been extensively studied in relation to CVD risk, however these studies have not always yielded consistent results, most likely due to lack in control of experimental conditions and confounding factors. Here we studied the effects of different plant and animal fats on dyslipidemia, inflammation and atherosclerosis. Ldlr-/-.Leiden mice were fed isocaloric energy-dense diets with translational macronutrient composition for 28 weeks. The diets were identical apart from the type of fat they contained: either 1) a mixture of olive and rapeseed oil; 2) sunflower oil; 3) pork fat; 4) beef fat; or 5) milk fat. The fatty acid composition of the diets was determined and effects on circulating lipid and inflammatory risk factors and atherosclerosis were examined, complemented by adipose tissue histology and liver transcriptomics. While visceral fat mass, adipocyte size and adipose tissue inflammation were not differentially affected by the diets, atherosclerotic lesion load and severity was more pronounced with increasing dietary saturated fatty acid content and decreasing monounsaturated and polyunsaturated fatty acid content, and hence most pronounced with beef and milk fat. These differential effects were accompanied by increases in pro-atherogenic plasma lipids/lipoproteins (e.g., triglycerides, apolipoprotein B), activation of pro-atherogenic cytokine/chemokine signaling pathways in liver, and with circulating pro-atherogenic mediators of inflammation altogether providing a rationale for the differential effects of plant and animal fats.
2023-12-21 | GSE232133 | GEO
Project description:Septic arthritis, most often caused by Staphylococcus aureus (S. aureus), is a rapidly progressive and destructive joint disease with substantial mortality and morbidity. S. aureus lipoproteins (Lpps) are known to induce arthritis and bone destruction. Here, we aimed to investigate the bone resorptive effect of S. aureus Lpps in a murine arthritis model by intra-articular injection of purified S. aureus Lpps, synthetic lipopeptides, and live S. aureus strains. Analyses of the bone mineral density of the distal femur bone were performed. Intra-articular injection of both live S. aureus and purified S. aureus Lpps were shown to significantly decrease total- and trabecular the bone mineral density. HPLC-high resolution MS/MS analyses revealed that the Lpps expressed by S. aureus SA113 strain contain both diacyl and triacyl lipid moieties. Therefore, tryptic digestion of Lpps was carried out, and the resulting lipopeptides were analyzed by HPLC-MS/MS, in which peptide fragments and neutral losses of fatty acids were used to identify the lipopeptide structures.
(doi: 10.3389/fmicb.2022.843799)
2022-01-27 | MSV000088739 | MassIVE
Project description:Intestinal lipid absorption, the entry-point for fats into the body, requires the coordinated actions of bile acids and lipases. Here, we uncover distinct yet cooperative roles of bile acids in driving the differential uptake of dietary fatty acids. We first decreased bile acid pool size by disrupting the rate-limiting enzyme in bile acid synthesis, Cyp7a1, using liver-directed gene editing in mice. Compared to lipase inhibition, reduced bile acids prevented diet-induced obesity, increased anorectic hormones, suppressed excessive eating, and improved systemic lipid metabolism. Remarkably, decreasing bile acids selectively decreased absorption of saturated fatty acids, but preserved polyunsaturated fatty acids. By targeting additional bile acid enzymes, we identified specific functions of individual bile acid species. Mechanistically, we show that cholic acid preferentially solubilizes polyunsaturated fatty acids into mixed micelles for intestinal uptake. Our studies demonstrate that bile acids can selectively control fatty acid uptake, revealing insights for future interventions in metabolic disease.
2025-11-17 | GSE304800 | GEO
Project description:Pancreatic cancer is a rare but fatal form of cancer, the fourth highest in absolute mortality. The main reason for the high mortality is late detection, caused in part by an incomplete understanding of the initiating factors. Known risk factors include obesity, diet and type 2 diabetes, however the low incidence rate and interconnection of these factors confound the isolation of individual effects from patient data. Here we use epidemiological analysis of prospective human cohorts and parallel tracking of pancreatic cancer in mice to dissect the impacts of obesity, diet and diabetes on pancreatic cancer development, growth and lethality. Through longitudinal magnetic resonance imaging and multi-omics analysis in mice we found distinct effects of obesity and the protein, sugar and fat composition of diet, and no added impact of diabetes. Using epidemiological approaches in humans, we found that dietary plant fats reduced the risk of future pancreatic cancer development, while dietary sugars gave a genotype-dependent increased susceptibility to pancreatic cancer. An interaction between MAD2L1 and dietary glucose in pancreatic cancer pathogenesis was supported through both genetic epidemiology in human patients and molecular analysis of mouse models. These results demonstrate that both quantitative and qualitative dietary effects are at play in pancreatic cancer kinetics, in both mice and humans. Translation of these results to a clinical setting could aid identification of theat-risk population for screening and potential harness dietary modification as a therapeutic measure.
2020-07-16 | E-MTAB-8227 | biostudies-arrayexpress
Project description:Nutrient limitation in the microenvironment of poorly perfused tumors constrains the metabolism of cancer cells. Identifying these microenvironmental constraints can provide new insight into the nutritional biochemistry of tumors and reveal metabolic liabilities of cancer cells. We have found that limitation of arginine in pancreatic cancers inhibits fatty acid synthesis by suppressing the lipogenic transcription factor SREBP1. SREBP1-driven fatty acid synthesis produces saturated and monounsaturated fatty acids. Producing these fatty acids enables cells to maintain a balance of differently saturated fatty acids needed for lipid homeostasis, even upon exposure to environments enriched in one specific class of fatty acids. Given the constraints on lipid synthesis in the microenvironment, we asked if pancreatic cancers are sensitive to exposure to fats with imbalanced levels of saturated and unsaturated fats. We found microenvironmental constraints on lipid synthesis sensitize pancreatic cancer cells and tumors to exposure to fat sources that are enriched in polyunsaturated fatty acids. Thus, amino acid restriction in the tumor microenvironment constrains lipid metabolism in pancreatic cancer, which renders pancreatic tumors incapable of maintaining lipid homeostasis upon exposure to polyunsaturated-enriched fats.
2025-02-11 | GSE288530 | GEO
Project description:Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the causative immune defect is unclear. We propose that high levels of LAIR2 in CTCL suppress LAIR1 inhibitory signaling, promoting inflammation and tissue damage, which increases S. aureus susceptibility. Mice do not have a LAIR2 homolog, so we used Lair1 KO mice to model LAIR2 overexpression. In a model of subcutaneous S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile immune stimulation, including increased production of proinflammatory cytokines and myeloid chemokines, neutrophil ROS, and collagen/ECM remodeling pathways. Notably, compared to WT, Lair1 KO infected skin had a similar bacterial burden and neutrophils and monocytes had equivalent S. aureus phagocytosis. These findings support a model in which lack of LAIR1 signaling results in an excessive inflammatory response that does not improve infection control. CTCL tissues harbored similar patterns of increased cytokine and collagen production, suggesting that high levels of LAIR2 in CTCL recapitulates Lair1 KO, causing inflammatory tissue damage and compromising host defense against S. aureus infection.
2024-07-31 | GSE269177 | GEO
Project description:Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the causative immune defect is unclear. We propose that high levels of LAIR2 in CTCL suppress LAIR1 inhibitory signaling, promoting inflammation and tissue damage, which increases S. aureus susceptibility. Mice do not have a LAIR2 homolog, so we used Lair1 KO mice to model LAIR2 overexpression. In a model of subcutaneous S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile immune stimulation, including increased production of proinflammatory cytokines and myeloid chemokines, neutrophil ROS, and collagen/ECM remodeling pathways. Notably, compared to WT, Lair1 KO infected skin had a similar bacterial burden and neutrophils and monocytes had equivalent S. aureus phagocytosis. These findings support a model in which lack of LAIR1 signaling results in an excessive inflammatory response that does not improve infection control. CTCL tissues harbored similar patterns of increased cytokine and collagen production, suggesting that high levels of LAIR2 in CTCL recapitulates Lair1 KO, causing inflammatory tissue damage and compromising host defense against S. aureus infection.
2024-07-31 | GSE269178 | GEO
Project description:S. aureus is a deadly pathogen due to its abilities to readily develop antibiotic resistance and evade our immune system. Antibiotic resistance in S. aureus is associated with reduced levels of neutrophil recruitment, which is a vital step in triggering an immune response to resolve infection. In this work, we report enhanced antibiotic agents that act as potential dual-function antibiotic-chemoattractants, enabling augmented neutrophil recruitment to S. aureus along with direct killing. Our agents exploit formylated peptides as chemoattractants for neutrophil recruitment, which is combined with the targeted binding of vancomycin to bacteria that generates a chemoattractant gradient for neutrophil recruitment. The combination of in vitro assays, cellular assays, infection-on-a-chip and in vivo mouse models, determined that these antibiotic-chemoattractants improve the recruitment, engulfment and killing of S. aureus by neutrophils. Furthermore, optimizing the fPep sequence can play an important role in the enhancement of neutrophil activity through differential activation of formyl peptide receptors. This offers an alternate approach in antibiotic development to overcome the threat of antibiotic resistance in the clinic.
2021-09-22 | PXD028332 | Pride