growth/size/body
• both 14-week-old male and female mice show a significant increase in whole body lean mass
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• male mutants do not show significant changes is body weight on a high-fat diet from 4 weeks of age compared to wild-type mice
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• on a normal chow diet, female mutants from 4 to 28 weeks of age have significantly increased body weights compared to wild-type (area under curve (AUC): wild-type, 505g/24 weeks vs Pyy-null, 554g/24 weeks)
• females show a marked increase in body weight between 15 and 28 weeks (AUC: mutants 344 g/15-28 weeks; wild-type 307.6 g/ 15-28 weeks)
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• female mutants, not males, develop late-onset obesity
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homeostasis/metabolism
• in regular chow-fed male mutants, serum testosterone levels are elevated to a statistically significant degree
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• male and female chow-fed animals show higher serum insulin levels than controls during glucose tolerance test period
• fasting and glucose-induced serum insulin levels are elevated significantly above those observed in wild-type mice fed a high fat diet (mutant >200 pmol/l/min vs wild-type ~150 pmol/l/min)
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• male mutants have significantly higher serum levels of IGF-1 when fed a normal chow diet
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• on a high-fat diet, male mutants are less glucose-tolerant than wild-type but difference disappears when data are normalized for bodyweight
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adipose tissue
• weight of all white fat adipose tissue deposits in females are increased at 28 weeks of age, consistent with increase in body fat
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• females show a decrease in whole body fat mass at 14 weeks
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• chow-fed females show a significant 50% increase in fat mass at 28 weeks of age
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• males fed on a high-fat diet from 4 weeks of age show significant increases in weight of gonadal white fat deposits
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behavior/neurological
N |
• mutants show no alterations in motor activity over a 14 day observation period
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nervous system
• 14-week old female mutants show a 51% increase in Pomc expression vs controls in the arcuate nucleus consistent with reduced food intake, while males show a 21% decrease in Npy expression and a 25% increase in Pomc, associated with increased lean mass and serum hormone levels; Ghrh is increased 32% in the ventromedial hypothalamic nucleus of mutants
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skeleton
• increase in lumbar bone mineral density and content in males and females
• increase in cancellous bone volume in the vertebral body in the females
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• significant increase in whole body BMC in females at 14 weeks of age
• increase in lumbar BMC in males and females
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• significant increase in whole body BMD in females at 14 weeks of age
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• increase in lumbar BMD in males and females
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• increase in cancellous bone volume in the lumbar vertebral body in the females
• increase in cancellous bone volume in the distal femoral metaphysis in males and females
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• increase in mineral apposition rate in the distal femoral metaphysis and in the mid femur
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