Analysis Tools
cellular
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• hepatocytes accumulate in S phase at late time points during culture compared to control hepatocytes which exit S phase
• hepatocytes accumulate in G2 phase in cultures at 60 hours after plating indicating a G2/M arrest
• treatment with the antioxidant NAC reduces accumulation of BrdU at 60 hours after plating, indicating normal progression through the cell cycle
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• high-calorie diet induces some hepatocyte apoptosis
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• markers of oxidative stress are detectable in hepatocytes both in vitro and in vivo
• treatment with the antioxidant NAC impairs the accumulation of ROS with no impact on cell viability
• long-term administration of NAC alleviates oxidative stress in the liver parenchyma
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growth/size/body
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• mice exhibit increased body weight at 3 months, but not 1 month, of standard chow diet
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• mice exhibit increased body weight when fed a high-calorie diet for 1 or 3 months
• body weight tends to be higher than in Leprdb homozygotes when fed a high-calorie diet
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homeostasis/metabolism
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N |
• mice do not exhibit an increase in plasma beta-hydroxybutyrate levels when fed a high-calorie diet
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• mice exhibit increased body weight when fed a high-calorie diet for 1 or 3 months
• body weight tends to be higher than in Leprdb homozygotes when fed a high-calorie diet
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• plasma non-esterified fatty acids (NEFAs) are increased after 1 month of a high-calorie diet, suggesting enhanced lipolysis
• however, plasma NEFAs are normalized after 3 months of high-calorie diet
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• total cholesterol levels are increased in mice fed a high-calorie diet for 1 month and 3 months
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liver/biliary system
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• hepatic necroinflammation is not prominent but tends to be detected more frequently than in Leprdb homozygotes after 1 month of standard chow but this trend is no longer seen after 3 months
• steatohepatitis is seen occasionally after 3 months of a standard diet but is not seen when mice are fed a high-calorie diet
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• mice develop steatosis, with steatosis mainly localized in the centrilobular and mediolobular areas
• steatosis is more severe than in Leprdb homozygotes whatever the diet, but the difference is most obvious after 1 month of standard chow
• mediovesicular steatosis is more frequently seen than in Leprdb homozygotes
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• macrovacuolar steatosis is similar to that seen in Leprdb homozygotes
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• some portal and perisinusoidal fibrosis is seen in standard diet fed mice at 3 months and is increased when mice are fed the high-calorie diet
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• livers are enriched in hepatocytes with high DNA content compared to controls
• binuclear fraction of hepatocytes is lower in the liver parenchyma
• the mononuclear diploid (2n) hepatocyte population is lower in the mutant liver than in wild-type liver while mononuclear tetraploid hepatocytes are enriched in the mutant liver
• liver contains highly polyploid mononuclear hepatocytes which are infrequently seen in wild-type liver
• treatment with the antioxidant NAC restores a normal ploidy profile in mutant cultures
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• high-calorie diet induces some hepatocyte apoptosis
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immune system
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• hepatic necroinflammation is not prominent but tends to be detected more frequently than in Leprdb homozygotes after 1 month of standard chow but this trend is no longer seen after 3 months
• steatohepatitis is seen occasionally after 3 months of a standard diet but is not seen when mice are fed a high-calorie diet
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| metabolic dysfunction-associated steatotic liver disease | DOID:0080208 |
OMIM:613282 OMIM:613387 |
J:277927 | |
| steatotic liver disease | DOID:9452 |
OMIM:228100 |
J:220381 | |
