Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA384630 | ENA |
REPOSITORIES: ENA
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Project description:ANGPTL4 regulates plasma triglyceride levels by inhibiting lipoprotein lipase. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in mesenteric lymph nodes. In mice these pathological events exclusively unfold upon feeding a high saturated fatty acid diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here we show that Angptl4-/- mice fed a diet rich in trans fatty acids develop numerous lipid-filled giant cells in their mesenteric lymph nodes, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a saturated fatty acid-rich diet. In RAW264.7 macrophages the saturated fatty acid palmitate markedly increases markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate have the opposite effect. In conclusion, trans and saturated fatty acids have very distinct biological effects. Furthermore, lipid accumulation in mesenteric lymph nodes is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.
2017-04-27 | GSE98303 | GEO
Project description:ANGPTL4 regulates plasma lipids, making it an attractive target for correcting dyslipidemia. However, ANGPTL4 inactivation in mice fed a high fat diet causes chylous ascites, an acute-phase response, and mesenteric lymphadenopathy. Here, we studied the role of ANGPTL4 in lipid uptake in macrophages and in the above-mentioned pathologies using Angptl4-hypomorphic and Angptl4-/- mice. Angptl4 expression in peritoneal and bone marrow-derived macrophages was highly induced by lipids. Recombinant ANGPTL4 decreased lipid uptake in macrophages, whereas deficiency of ANGPTL4 increased lipid uptake, upregulated lipid-induced genes, and increased respiration. ANGPTL4 deficiency did not alter LPL protein levels in macrophages. Angptl4-hypomorphic mice with partial expression of a truncated N-terminal ANGPTL4 exhibited reduced fasting plasma triglyceride, cholesterol, and non-esterified fatty acid levels, strongly resembling Angptl4-/- mice. However, during high fat feeding, Angptl4-hypomorphic mice showed markedly delayed and attenuated elevation in plasma serum amyloid A and much milder chylous ascites than Angptl4-/- mice, despite similar abundance of lipid-laden giant cells in mesenteric lymph nodes. In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice.
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2023-06-07 | GSE230558 | GEO
Project description:To fully quantify differences in the lymph composition and associated dendritic cells antigenic load, from different anatomical districts and in physiological and pathological conditions, we collected the afferent lymph draining to the cervical and mesenteric lymph nodes in healthy mice. Most of the proteome present in the mesenteric afferent lymph, showed a profile of proteins involved in different metabolic pathways associated with lipoproteintransport, and lipid metabolism, such as adipocyte-type fatty acid binding protein, Apolipoproteins A, B, C and E, and phospholipid transfer proteins, consistent with the known role of the mesenteric lymph in chylomicron transport. Network analysis on the mesenteric afferent lymph unique/enriched proteome highlighted pathways associated with lipase and hydrolase activity, lipoproteins remodeling, fat digestion and absorption, triglyceride catabolism and gut-associated immune cells and cytokines responses. Among the proteome shared across tissue a brain-specific or highly enriched proteome including glia maturation factor, nerve growth factor, mesencephalic astrocyte-derived neurotrophic factor, alpha-crystallin, brain-specific isoform of glycogen phosphorylase, and proteins associated with voltage-dependent channels, were uniquely observed in the lymph harvested from the afferent lymphatics entering the deep cervical nodes. Network analysis on the afferent cervical unique/enriched proteome highlighted pathways associated with neurotransmitter release cycle, synaptic transmission, neuronal development, mitochondrial activity, and an overall CNS proteome.
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2009-04-23 | GSE15748 | GEO
Project description:Normal gene expression in pancreatic lymph nodes compared to inguinal or mesenteric lymph nodes across different strains of mice (BALB/c, FVB, NOD, NOD.B10). Lymph nodes were excised from 12 wk old female mice (5 mice per group), and total RNA was extracted for dual dye microarray analysis.
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Project description:The mesenteric lymph nodes represent the immune response to eggs in schistosome infections,and the analysis of gene expression profiles of the mesenteric lymph nodes from the Vac-Cha (vaccinated with UV attenuated cercariae and challenged with normal cercariae)and Inf-Con (infected with normal cercariae) groups. We used microarrays to detail the global programme of gene expression and identified distinct classes of up-regulated and down-regulated genes.
2010-06-11 | GSE22311 | GEO