Analysis Tools
mortality/aging
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• 20-30% of homozygotes die before weaning; whether lethality occurs in utero or neonatally (or both) has not been determined
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growth/size/body
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• normal gain weight and body composition after 8 weeks on a high-fat diet (60% kJ/fat), indicating normal diet-induced obesity relative to wild-type controls
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• surviving mice maintained on a standard chow diet show increased fat mass at 9 weeks of age
• 50% increase in fat mass at 24 weeks of age, with no significant differences in body weight or fat-free mass
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• on a standard chow diet, surviving mice show a significant increase in body weight solely due to increased fat mass
• chow-fed males are heavier than females at 9 weeks of age
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adipose tissue
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• surviving mice maintained on a standard chow diet show increased fat mass at 9 weeks of age
• 50% increase in fat mass at 24 weeks of age, with no significant differences in body weight or fat-free mass
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• on a standard chow diet, mice show increased adiposity (fat mass as a % of total body weight) at 9 weeks, but not 6 weeks of age
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homeostasis/metabolism
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• at 8-10-weeks of age, chow-fed mice show hyperglycemia after an overnight fast; however, mice are not glucose intolerant
• significantly more severe fasting hyperglycemia associated with weight gain after 8 weeks on a high-fat diet relative to wild-type controls
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• at 8-10-weeks of age, chow-fed mice show mild hyperinsulinemia after an overnight fast
• significantly more severe fasting hyperinsulinemia associated with weight gain after 8 weeks on a high-fat diet relative to wild-type controls
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• at 8-10-weeks of age, chow-fed mice show increased triglyceride levels after an overnight fast
• significantly increased fasting triglyceride levels associated with weight gain after 8 weeks on a high-fat diet relative to wild-type controls
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• glucose tolerance is more severely impaired after 8 weeks on a high-fat diet relative to wild-type controls
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• significantly lower glucose infusion rate in hyperinsulinemic-euglycemic clamp conditions relative to wild-type controls
• marked (75-80%) reduction in the ability of insulin to suppress endogenous glucose production in clamp conditions, suggesting insulin resistance
• however, insulin stimulation of Akt phosphorylation is normal in liver
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• significantly increased liver triglyceride content after 8 weeks on a high-fat diet relative to wild-type controls
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• significantly increased hepatic expression of stearoyl-CoA desaturase-1 (SCD1) and sterol-regulatory element binding protein-1c (SREBP1C) after 8 weeks on a high-fat diet relative to wild-type controls
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behavior/neurological
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• chow-fed mice show a modest but significant reduction in physical activity (X-beam breaks/h) in the dark phase at 8 weeks of age
• however, the respiratory exchange ratio, energy expenditure, and food intake are normal
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liver/biliary system
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• significantly increased liver triglyceride content after 8 weeks on a high-fat diet relative to wild-type controls
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• significantly increased total lipid content in liver after 8 weeks on a high-fat diet relative to wild-type controls
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muscle
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• insulin-stimulated glucose uptake is decreased by 30-35% in gastrocnemius and diaphragm muscle
• however, glucose uptake in other muscle types (soleus, vastus lateralis, cardiac muscle), brain, and adipose tissue is normal
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cellular
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• insulin-stimulated glucose uptake is decreased by 30-35% in gastrocnemius and diaphragm muscle
• however, glucose uptake in other muscle types (soleus, vastus lateralis, cardiac muscle), brain, and adipose tissue is normal
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