growth/size/body
• males weigh 10% less than wild-type males at 30 weeks; by 52 weeks of age, males weigh 17% less than wild-type males
• females weigh 14% less than wild-type females at 30 weeks of age
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• starting at 20 weeks of age, homozygotes fed a standard chow diet exhibit an age-related decrease in the rate of weight gain relative to wild-type controls
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behavior/neurological
• ~28% increase in food intake, expressed as cumulative food intake in grams per g of body weight, starting from 20 weeks to 28 weeks of age
• at 30 weeks of age, food intake per animal per day is 14% more than that of wild-type males, despite a 10% reduction in weight gain
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adipose tissue
• at 30 weeks of age, mice have less subcutaneous fat than wild-type controls
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• at 30 weeks of age, mice are leaner and have less fat surrounding internal organs than wild-type controls
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• at 30 weeks of age, the diameter of epididymal WAT adipocytes is less than that of wild-type, representing a 62% reduction in cell volume
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• lack of increase in fat depot size as mice age, unlike in wild-type controls
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• at 30 weeks of age, epididymal fat pads weigh 63% less than those of wild-type males
• the ratio of epididymal white adipose tissue (EWAT) weight to body weight remains relatively constant with age, unlike in wild-type controls, and at 30 weeks of age it is 56% less than that of wild-type males
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• at 30 weeks of age, mice have less inguinal fat than wild-type controls
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homeostasis/metabolism
• at 20 weeks of age, the rate of oxidation of [14C]palmitate in resting skeletal (soleus) muscle is 32% lower than that of wild-type controls
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• at 20 weeks of age, the rate of oxidation of [14C]palmitate in epididymal white adipose tissue (EWAT) is 55% more than that of wild-type controls
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• at 30 weeks of age, total plasma cholesterol level in males remains constant and is ~24% less than that in wild-type males; females show a lower total plasma cholesterol level than wild-type females
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• at 30 weeks of age, mice show a 34% decrease in plasma HDL levels relative to wild-type controls
• however, the ratio of total cholesterol to HDL is normal
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• at 30 weeks of age, mice show a 25% decrease in plasma LDL levels relative to wild-type controls
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• resting energy expenditure (REE), a measure of basal metabolic rate plus energy expended in processing food, is higher than in wild-type controls
• >80% of increased whole-body energy expenditure is due to increased REE
• however, no increase in voluntary wheel running (physical activity) is noted at 30 weeks of age
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• significantly higher oxygen consumption than wild-type mice during both the light and dark phases
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• significantly increased RER during the dark but not during the light phase relative to wild-type controls, indicating a switch from fat to carbohydrate oxidation
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• at 30 weeks of age, the plasma concentration of pyruvate is 57% lower than that in wild-type controls
• however, plasma concentration of pyruvate is normal at 15 weeks of age
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• at 30 weeks but not at 10 weeks of age, both males and females exhibit significantly lower plasma glucose levels than age-matched wild-type controls
• however, no differences in urine glucose levels or in liver glycogen content are observed
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• at 30 weeks of age, mice exhibit a significantly lower plasma glucose level than wild-type controls after a 12-hr fast
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• decreased accumulation of triglycerides in WAT at 30 weeks of age
• however, plasma level of triglycerides, non-esterified fatty acids , and glycerol are normal, indicating normal lipid import into or export from adipocytes
• no signs of ectopic fat storage in liver, suggesting normal export of triglycerides from liver
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• downregulation of proteins involved in carbohydrate metabolism in the liver relative to wild-type controls
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• downregulation of proteins involved in in cholesterol or lipid synthesis in the liver relative to wild-type controls
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cellular
• at 20 weeks of age, the rate of oxidation of [14C]palmitate in resting skeletal (soleus) muscle is 32% lower than that of wild-type controls
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• at 20 weeks of age, the rate of oxidation of [14C]palmitate in epididymal white adipose tissue (EWAT) is 55% more than that of wild-type controls
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integument
• at 30 weeks of age, mice have less subcutaneous fat than wild-type controls
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