growth/size/body
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• reduced fat mass in both sexes at 12 weeks of age, as revealed by body composition analysis (EchoMRI)
|
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• slightly increased lean mass in both sexes at 12 weeks of age, as revealed by EchoMRI
|
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• increased body weight in both sexes at 9 and 12 weeks of age, but not at 3 or 6 weeks of age
• however, food intake is not significantly altered
|
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• enlarged liver at 12 weeks of age
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• markedly increased liver weight at 12 weeks of age
|
adipose tissue
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• reduced fat mass in both sexes at 12 weeks of age, as revealed by body composition analysis (EchoMRI)
|
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• brown adipose tissue (BAT) contains many white-adipocyte-like unilocular cells, indicating whitening of brown fat
• however, no change in brown adipose tissue (BAT) mass at 3 or 12 weeks of age
|
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• severely reduced gonadal white fat depot (gWAT) weight in males as early as 3 weeks of age
|
|
• severely reduced inguinal white fat depot (iWAT) weight in males as early as 3 weeks of age
|
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• reduction in mesenteric WAT (mWAT) weight at 12 weeks of age
|
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• reduction in retroperitoneal WAT (rWAT) weight at 12 weeks of age
|
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• interscapular BAT is much paler at 12 weeks of age, resembling WAT
|
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• small amount of residual WAT appears unhealthy with sparse, irregularly sized adipocytes among a fibrous extracellular matrix
|
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• reduction in anterior subcutaneous WAT (asWAT) weight at 12 weeks of age
|
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• sparse white adipocytes
|
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• irregularly sized white adipocytes
|
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• dramatic reduction in white adipose tissue mass at 12 weeks of age
• however, no change in brown adipose tissue (BAT) mass at 3 or 12 weeks of age
|
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• mRNA expression of BAT genes, including Ucp1, is reduced
|
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• gene expression analysis of gWAT and iWAT revealed reduced mRNA levels of the adipocyte genes aP2, C/EBPalpha, and PPARgamma; mRNA expression of C/EBPbeta and KLF5 is either unchanged or elevated
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homeostasis/metabolism
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• both sexes are hyperglycemic
|
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• markedly increased fasting serum insulin levels
|
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• both sexes are glucose intolerant
|
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• impaired response to insulin in insulin tolerance test
|
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• 4-fold increase in liver triglyceride content
|
liver/biliary system
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• enlarged liver at 12 weeks of age
|
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• markedly increased liver weight at 12 weeks of age
|
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• 4-fold increase in liver triglyceride content
|
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• massive accumulation of lipid droplets in liver at 12 weeks of age
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pale liver
(
J:298822
)
|
• pale liver at 12 weeks of age
|
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• impaired hepatic insulin signaling, as assessed by phosphorylation of Akt in response to insulin
|
integument
|
• reduction in anterior subcutaneous WAT (asWAT) weight at 12 weeks of age
|


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