growth/size/body
• male and female mice show about 7% greater lean mass than wild-type controls at 5-7 months
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• females maintained on a high-fat diet for 7 weeks gain significantly more weight than wild-type females maintained on regular chow, but weight gain is the same as mutant females fed regular chow for the same period
• resistance to diet-induced obesity is due to hyperactivity and increased energy expenditure
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homeostasis/metabolism
N |
• plasma glucose, insulin, and triglyceride level are not different from controls in 5-7 month old males
• mice show normal responses to orexigenics (NPY, AgRP); chronic melanin-concentrating hormone administration (6 days) has no effect on mutants, whereas wild-type mice show significant increases in food intake, weight gains, and altered body compositions
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• females maintained on a high-fat diet for 7 weeks gain significantly more weight than wild-type females maintained on regular chow, but weight gain is the same as mutant females fed regular chow for the same period
• resistance to diet-induced obesity is due to hyperactivity and increased energy expenditure
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• significantly lower in male mutants during light phase, whereas RQ is comparable to wild-type mice during light phase
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• corticotrophin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus are significantly lower in males relative to wild-type, but are normal in the central nucleus of the amygdala
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• levels are significantly lower in males compared to wild-type at 5-7 months; similar trend is observed in females
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• 6-7 month-old males have significantly greater plasma corticosterone levels than wild-type
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• levels are significantly lower in males compared to wild-type at 5-7 months; similar trend is observed in females
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• mice have significantly greater metabolic rate during part of the dark phase, correlating with the period of hyperactivity
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behavior/neurological
• hyperphagia is accompanied by increased drinking behavior (increased duration)
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polyphagia
(
J:81787
)
• animals exhibit hyperphagia (15.8% and 12.3% greater food intake by males and females, respectively) on regular mouse chow and when group- or individually-housed; hyperphagia in the range of 12-24% is consistently observed
• hyperphagia is result of significantly increased eating duration; behavior is restricted entirely to dark phase of light-dark cycle
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• mice are 2x more active during dark phase compared to controls, but show normal levels of ambulatory activity during light phase; mice exhibit significantly more fine motor movements during dark phase relative to wild-type
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adipose tissue
• male and female mice have about 50% less fat mass than wild-type at 5-7 months
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