liver/biliary system
• in the nourished state, mutant livers contain 20% less glycogen than wild-type livers
• in the 24-hr-fasted state, wild-type livers contain abundant glycogen, whereas mutant livers contain very little or no detectable glycogen
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• mutant livers contain 80-90% less triglycerides than wild-type livers
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adipose tissue
• homozygotes contain a reduced amount of white fat under their skin (33.6 g weight) relative to wild-type (34.2 g weight)
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• on average, homozygotes accumulate 50% less fat in their adipose tissues than wild-type
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behavior/neurological
polyphagia
(
J:68427
)
• on average, homozygotes fed a standard diet ad liberatum consume 20-30% more food than wild-type mice
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cellular
• homozygotes exhibit a significant increase in mitochondrial beta-oxidation of fatty acids in the skeletal muscle
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• in the mutant soleus muscle, the fatty acid oxidation rate is 30% higher and is not affected by addition of insulin; in contrast, addition of insulin to wild-type muscle reduces fatty acid oxidation by 45%
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growth/size/body
• when fed a standard diet ad liberatum, homozygotes weigh about 10% less than wild-type mice
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homeostasis/metabolism
• on a standard diet, homozygotes exhibit a 20% reduction in serum glucose levels relative to wild-type
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• homozygotes display a 30% reduction in plasma leptin relative to wild-type
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• although hyperphagic, homozygotes are able to maintain or even lose body weight, suggesting that they expend energy at an increased rate
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• homozygotes exhibit 10- and 30-fold lower levels of malonyl-CoA in heart and skeletal muscle, respectively
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• in the nourished state, mutant livers contain 20% less glycogen than wild-type livers
• in the 24-hr-fasted state, wild-type livers contain abundant glycogen, whereas mutant livers contain very little or no detectable glycogen
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• mutant livers contain 20% less lipid than wild-type livers
• despite their lipid store depletion, homozygotes appear grossly normal, grow at the expected rate, and breed normally
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• homozygotes exhibit a significant increase in mitochondrial beta-oxidation of fatty acids in the skeletal muscle
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• in the mutant soleus muscle, the fatty acid oxidation rate is 30% higher and is not affected by addition of insulin; in contrast, addition of insulin to wild-type muscle reduces fatty acid oxidation by 45%
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• on a standard diet, serum levels of the ketone bodies (beta-hydroxybutyrate) are nearly absent in both wild-type and mutant mice
• in homozygotes, an overnight fast results in a 4-fold increase in the serum levels of ketone bodies, consistent with a higher fatty acid oxidation rate
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• on a standard diet, homozygotes display a 30% increase in serum triglyceride levels relative to wild-type
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• in mutants, fatty acid stores in adipose tissue and liver are significantly reduced (in adipose tissue by 50%), despite normal concentrations of malonyl-CoA
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• on a standard diet, homozygotes display a reduction in serum free fatty acid levels relative to wild-type mice
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• mutant livers contain 80-90% less triglycerides than wild-type livers
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integument
• homozygotes contain a reduced amount of white fat under their skin (33.6 g weight) relative to wild-type (34.2 g weight)
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