Analysis Tools
homeostasis/metabolism
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• reduced lipid oxidation during the dark phase in chow-fed mice
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• after only 8 weeks on a high fat/high cholesterol diet (HF/HCD), mice weigh up to 8 g (35% of body weight) less than control mice
• after 20 weeks of HF/HCD feeding, mice show a 68% reduction in perigonadal white adipose tissue (WAT) weight relative to control mice
• however, food intake, daily locomotor activity, energy expenditure, and fecal energy content are unchanged on a HF/HCD
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• increased plasma beta-hydroxybutyrate concentrations after 10 weeks of HF/HCD feeding, indicating a shift toward ketone body formation for energy supply
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• increased plasma total cholesterol (TC) concentrations in 12 h-fasted mice
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• increased plasma LDL but normal HDL cholesterol concentrations in 12 h-fasted mice
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• 28-fold increase in plasma alanine aminotransferase (ALT) concentrations after 10 weeks of HF/HCD feeding, indicating liver damage
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• 11-fold increase in plasma aspartate aminotransferase (AST) concentrations after 10 weeks of HF/HCD feeding, indicating liver damage
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• mice fed a regular chow diet exhibit a higher respiratory exchange ratio than control mice
• however, energy expenditure, food intake and daily physical activity are unchanged on a chow diet
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• significant reduction of hepatic mRNA expression of several genes involved in gluconeogenesis (including Pepck and G6Pase) after 20 weeks of HF/HCD feeding
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• improved glucose clearance during glucose tolerance tests after 10 weeks of HF/HCD feeding
• however, glucose tolerance is not altered in chow diet-fed mice
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• after 12 weeks of HF/HCD feeding, mice show a significant drop and delay in the normalization of blood glucose levels following an insulin challenge, indicating increased insulin sensitivity
• however, insulin sensitivity is not altered in chow diet-fed mice
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• 8-fold increase of hepatic cholesteryl ester (CE) concentrations in 12 h-fasted mice, with increased neutral lipid staining, as determined by Oil Red O (ORO) staining
• 6.9-fold increase of hepatic CE concentrations after 10 weeks of HF/HCD feeding
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• unsaturated fatty acid species 16:1, 18:1, 18:2, 20:4 and 22:6 are reduced by >50% in the hepatic diacylglycerol (DG) and triglyceride (TG) fractions of HF/HCD-fed mice
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• all fatty acid species are increased in the hepatic cholesteryl ester (CE) fraction of HF/HCD-fed mice with most notable changes seen in 18:0, 18:1, 18:2, 20:4, and 22:6
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• liver diacylglycerol (DG) and triglyceride (TG) concentrations are reduced by 40% and 62%, respectively, after 10 weeks of HF/HCD feeding
• despite reduction of hepatic TG concentrations in HF/HCD-fed mice, VLDL secretion after inhibition of peripheral lipolysis by tyloxapol is unchanged
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• increased carbohydrate oxidation during both the light and dark phases in chow-fed mice
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• 70% reduction in lysosomal acid lipase (LAL) activity in hepatocytes, with complete absence of LAL protein expression in isolated hepatocytes
• 90% reduction of cholesteryl ester (CE) hydrolase activity in hepatocytes at an acidic pH 4
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• 70% reduction of triglyceride (TG) hydrolase activity in hepatocytes at an acidic pH 4
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liver/biliary system
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• increased liver size in HF/HCD-fed mice
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• increased total liver mass as well as liver mass relative to body weight after 10 weeks of HF/HCD feeding
• however, body weight and total liver mass are normal in chow diet-fed mice
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• 8-fold increase of hepatic cholesteryl ester (CE) concentrations in 12 h-fasted mice, with increased neutral lipid staining, as determined by Oil Red O (ORO) staining
• 6.9-fold increase of hepatic CE concentrations after 10 weeks of HF/HCD feeding
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• liver diacylglycerol (DG) and triglyceride (TG) concentrations are reduced by 40% and 62%, respectively, after 10 weeks of HF/HCD feeding
• despite reduction of hepatic TG concentrations in HF/HCD-fed mice, VLDL secretion after inhibition of peripheral lipolysis by tyloxapol is unchanged
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• hepatic macrophage infiltration and increased hepatic mRNA expression levels of liver injury markers, chemokines and cytokines after 20 weeks of HF/HCD feeding, indicating liver inflammation
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• increased cholesteryl ester (CE) crystal formation in the cytoplasm of hepatocytes after 10 weeks of HF/HCD feeding
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• livers show lysosomal neutral lipid accumulation with only few cytosolic lipid droplets after 10 weeks of HF/HCD feeding
• liver lipid droplets are predominantly smaller in size resulting in a reduced total lipid droplet area in HF/HCD-fed mice
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• increased collagen content after 20 weeks of HF/HCD feeding, indicating liver fibrosis
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pale liver
(
J:270182
)
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• discolored livers in HF/HCD-fed mice
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immune system
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• hepatic macrophage infiltration and increased hepatic mRNA expression levels of liver injury markers, chemokines and cytokines after 20 weeks of HF/HCD feeding, indicating liver inflammation
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adipose tissue
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• both white and brown adipocyte size and cell appearance are normal in mice fed a high fat/high cholesterol diet (HF/HCD)
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• after 20 weeks of HF/HCD feeding, mice show a 68% reduction in perigonadal WAT weight relative to control mice
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cellular
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• significant reduction of hepatic mRNA expression of tricarboxylic acid cycle genes after 20 weeks of HF/HCD feeding
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• reduced lipid oxidation during the dark phase in chow-fed mice
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growth/size/body
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• after only 8 weeks on a high fat/high cholesterol diet (HF/HCD), mice weigh up to 8 g (35% of body weight) less than control mice
• after 20 weeks of HF/HCD feeding, mice show a 68% reduction in perigonadal white adipose tissue (WAT) weight relative to control mice
• however, food intake, daily locomotor activity, energy expenditure, and fecal energy content are unchanged on a HF/HCD
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• increased liver size in HF/HCD-fed mice
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• increased total liver mass as well as liver mass relative to body weight after 10 weeks of HF/HCD feeding
• however, body weight and total liver mass are normal in chow diet-fed mice
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