growth/size/body
• 4-month-old mice weaned onto a high fat diet have significantly higher lean mass than heterozygous or wild-type littermates
• at 4 months, males have a greater amount of lean mass than females
• male and female animals fed a high fat diet increase total lean by mass by 10-20% compared to mice maintained on a normal chow diet
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• at 10-11 months of age, high fat diet (HFD)-fed homozygotes have lower average weight (42.0g) compared to HFD-fed heterozygous controls (51.5g)
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homeostasis/metabolism
• leptin levels in HFD-fed males and females are decreased 3.4- and 9.7-fold compared to HFD-fed controls
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• HFD-fed homozygous males have 15-20% lower plasma cholesterol levels than HFD-fed heterozygous or wild-type controls; no difference was observed in HFD-fed female homozygotes
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• HFD-fed homozygous males have 15-20% lower plasma triglyceride levels than HFD-fed heterozygous or wild-type controls; no difference was observed in HFD-fed female homozygotes
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• male homozygotes have higher plasma TNF alpha levels than females
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• levels are reduced about 40% in HFD-fed males compared to HFD-fed heterozygous males
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• in HFD-fed mutants, glucose disposal rate (GDR) upon insulin stimulation is enhanced 200 to 400% compared to HFD-fed heterozygotes
• basal GDR is similar between HFD-fed homozygotes and heterozygotes
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• females have lower basal glucose levels than than heterozygous or wild-type littermates
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• females and males display lower basal insulin levels than heterozygous or wild-type littermates
• HFD-fed males and females have 3.5 and 2.5-fold lower plasma insulin levels than heterozygous or wild-type controls
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• hepatic glucose production (HPG) is enhanced by 200-400% in HFD-fed homozygotes compared to heterozygotes
• basal HPG is similar between HFD-fed homozygotes and heterozygotes
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• plasma insulin levels after glucose loading are markedly reduced after glucose loading in HFD-fed mice compared to HFD-fed heterozygous controls
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• in response to direct insulin challenge, HFD-fed males have lower blood glucose levels at 20, 40 and 60 minutes compared to heterozygous males; HFD-fed females have lower blood glucose levels than heterozygous females at 60 and 80 minutes after insulin challenge
• whole-body insulin sensitivity is maintained in HFD-fed homozygotes at 10-11 months of age
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• HFD-fed males and females show improved insulin resistance compared to HFD-fed heterozygous controls
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• in chow-fed homozygotes, adiponectin levels are 2-3 fold lower than controls; HFD-fed males display decreased adiponectin levels whereas HFD-fed females showed a trend toward increased levels compared to heterozygous controls
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adipose tissue
• on a HFD, 10-11 month-old mutant fat pads weigh 3-4-fold less than HFD-fed heterozygotes
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• mice remain lean with high fat feeding, in contrast than heterozygous or wild-type littermates; 4-month-old mice weaned onto a high fat diet (HFD) have lower fat mass than heterozygous or wild-type littermates
• at 4 months, males have a signicantly lower amount of fat mass than females
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muscle
• quadriceps weigh 1.4-fold more than those of HFD-fed heterozygotes
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• gastrocnemius muscle weighs 1.4-fold more than that of HFD-fed heterozygotes
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liver/biliary system
• livers of 10-11 month old HFD-fed homozygotes show no evidence of hepatic steatosis whereas livers of HFD-fed heterozygotes exhibit large vacuoles and lipid droplets
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immune system
• male homozygotes have higher plasma TNF alpha levels than females
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• levels are reduced about 40% in HFD-fed males compared to HFD-fed heterozygous males
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limbs/digits/tail
• quadriceps weigh 1.4-fold more than those of HFD-fed heterozygotes
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• gastrocnemius muscle weighs 1.4-fold more than that of HFD-fed heterozygotes
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