Analysis Tools
adipose tissue
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• at 10-12 months, homozygotes exhibit a normal food intake but show a ~60% reduction in overall WAT weight
• in contrast, intercapsular BAT weight and heart weight remains unaffected
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• at 10-12 months, male and female homozygotes exhibit reduced adipose tissue mass relative to wild-type counterparts
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• at 10-12 months, male homozygotes display 35% of wild-type reproductive fat pad weights
• however, no differences in epididynal WAT histology are observed
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• at 10-12 months, male and female homozygotes display 42% and 53% of wild-type inguinal fat pad weights, respectively
• in males, the inguinal WAT displays the characteristic multilocular appearance of brown adipocytes, and shows a ~6-fold increase in mRNA expression of UCP1, a specific marker of brown fat
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• at 10-12 months, male and female homozygotes display 36% and 53% of wild-type retroperitoneal fat pad weights, respectively
• in males, the retroperitoneal WAT displays the characteristic multilocular appearance of brown adipocytes
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• male homozygotes display histologic, physiologic and molecular features of brown adipocytes in their inguinal WAT, including upregulation of UCP1 expression and increased protein levels of a transcriptional co-activator implicated in mitochondrial biogenesis and adaptive thermogenesis
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homeostasis/metabolism
hypoglycemia
(
J:72217
)
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• homozygotes are viable, fertile, and developmentally normal with no signs of illness or tumor formation
• however, homozygotes exhibit a ~15% reduction in fed and fasted glycemia, despite normal plasma insulin levels
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• male homozygotes show a 60% reduction in circulating leptin levels relative to wild-type males
• in contrast, circulating triglyceride levels remain unaffected
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• male homozygotes exhibit a ~15% increase in their metabolic rate (ml 02/kg/h) relative to wild-type males
• in contrast, female homozygotes show a normal metabolic rate relative to wild-type females
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growth/size/body
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• at 9-10 weeks, male homozygotes show a normal linear (nose-anus) growth; however, mutant males display a ~10% reduction in body weight relative to wild-type males
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cellular
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• mutant MEFs exhibit increased eIF4E phosphorylation relative to wild-type MEFs
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