Analysis Tools
liver/biliary system
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• males fed a MASH diet show reduced abundance of apoptotic cells in the liver compared to controls
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• livers of male mice fed a MASH diet show decreased liver fibrosis, a reduction of monocyte-derived macrophages (MDMs) and nonalcoholic steatohepatitis associated macrophages (NAMs), and increased percentage of HSCs that display a quiescent phenotype
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• mice are protected from diet-induced metabolic dysfunction-associated steatohepatitis (MASH; formerly nonalcoholic steatohepatitis)
• mice fed a MASH diet (40 kcal % fat, 20 kcal % fructose, and 2% cholesterol) show lower plasma AST and ALT levels, deceased liver fibrosis, reduced apoptosis in the liver, lower plasma TNF-alpha and CCL2 levels, reduced monocyte-derived macrophages and nonalcoholic steatohepatitis associated macrophages in the liver, and increased percentage of HSC in the liver that display a quiescent phenotype
• mice fed a choline-deficient, methionine-restricted high-fat diet (CDA-HFD) show reduced liver fibrosis and TNF-alpha and CCL2 abundance
• however, plasma AST and ALT concentrations in mice fed a CDA-HFD diet are similar to controls
• mice fed a MASH diet and treated with lipid droplets daily show blunted plasma ALT and AST concentrations compared to controls, indicating reduced liver injury compared to controls
• however, on the MASH diet, males gain comparable body weight, have similar plasma lipid and glucose concentrations and whole-body insulin sensitivity, liver weight and hepatic steatosis as wild-type mice on the MASH diet
• MASH-diet fed mice treated with MCC950, a selective inhibitor of the NLRP3 inflammasome, fail to further improve MASH pathology
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cellular
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• males fed a MASH diet show reduced abundance of apoptotic cells in the liver compared to controls
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hematopoietic system
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• livers of male mice fed a MASH diet show a reduction of monocyte-derived macrophages (MDMs) and nonalcoholic steatohepatitis associated macrophages (NAMs)
• the percentage of macrophages displaying a NAM gene signature is reduced in MASH fed mice and the abundance of GPNMB+CD9+ NAMs is reduced
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• a higher percentage of hematopoietic stem cells (HSCs) from livers of mice fed the MASH diet display a quiescent phenotype compared to controls
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• apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation is greatly reduced in BMDMs primed with LPS and treated with ATP
• BMDMs show diminished calcium response to ATP exposure
• primary liver macrophages isolated from MASH-fed mice show impaired NLRP3 inflammasome activation and IL-1beta release
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homeostasis/metabolism
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• males fed a MASH diet show lower plasma TNF-alpha levels
• mice fed a choline-deficient, methionine-restricted high-fat diet (CDA-HFD) show reduced TNF-alpha levels
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• males fed a MASH diet show lower plasma alanine transaminase (ALT) concentration compared to controls
• however, plasma ALT concentration in mice fed a CDA-HFD diet are similar to controls
• mice fed a MASH diet and treated with lipid droplets daily show blunted plasma ALT concentration compared to controls, indicating reduced liver injury compared to controls
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• males fed a MASH diet show lower plasma aspartate transaminase (AST) concentration compared to controls
• however, plasma AST concentration in mice fed a CDA-HFD diet are similar to controls
• mice fed a MASH diet and treated with lipid droplets daily show blunted plasma AST concentration compared to controls, indicating reduced liver injury compared to controls
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• males fed a MASH diet show lower plasma CCL2 levels
• mice fed a choline-deficient, methionine-restricted high-fat diet (CDA-HFD) show reduced CCL2 levels
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immune system
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• livers of male mice fed a MASH diet show a reduction of monocyte-derived macrophages (MDMs) and nonalcoholic steatohepatitis associated macrophages (NAMs)
• the percentage of macrophages displaying a NAM gene signature is reduced in MASH fed mice and the abundance of GPNMB+CD9+ NAMs is reduced
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• apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation is greatly reduced in BMDMs primed with LPS and treated with ATP
• BMDMs show diminished calcium response to ATP exposure
• primary liver macrophages isolated from MASH-fed mice show impaired NLRP3 inflammasome activation and IL-1beta release
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• males fed a MASH diet show lower plasma TNF-alpha levels
• mice fed a choline-deficient, methionine-restricted high-fat diet (CDA-HFD) show reduced TNF-alpha levels
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• males fed a MASH diet show lower plasma CCL2 levels
• mice fed a choline-deficient, methionine-restricted high-fat diet (CDA-HFD) show reduced CCL2 levels
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• bone marrow derived macrophates (BMDMs) primed with lipopolysaccharide (LPS) followed by ATP treatment (to induce inflammasome activation) show diminished IL-1beta release by macrophages compared to controls which show stimulation of IL-1beta release
• primary liver macrophages isolated from MASH-fed mice show impaired NLRP3 inflammasome activation and IL-1beta release
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