growth/size/body
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• female, but not male, homozygotes are protected from diet-induced obesity
• when fed a high-fat diet (HFD) starting at 10 wks of age, female homozygotes begin to gain less weight than wild-type controls, with the difference in body weight reaching statistical significance in the 18th wk of high-fat feeding
• after 30 wks on a HFD, the weight of female homozygotes is 11% lower than that of wild-type controls, largely due to a reduction in fat mass
• in contrast, male homozygotes fed a HFD show no differences in weight gain relative to wild-type controls
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• after 40 wks on a HFD, both male and female homozygotes show significantly increased liver weight relative to wild-type controls
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homeostasis/metabolism
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• on a low-fat standard chow diet, male homozygotes exhibit normal levels of nonesterified fatty acids, ketones (beta-hydroxybutyrate), triglycerides, glucose, and transaminases (ALT and AST) relative to wild-type controls
• overnight-fasted male homozygotes show no significant changes in any of these parameters relative to fasted wild-type controls
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• after 30 wks on a HFD, both male and female homozygotes show significantly lower fed blood glucose levels than sex-matched wild-type controls
• however, fasted glucose levels as well as insulin levels in both fed and fasting conditions are not significantly altered
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• on a low-fat standard chow diet, male homozygotes show a significant decrease in total plasma cholesterol levels relative to wild-type controls
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• after 40 wks on a HFD, both male and female homozygotes show significantly increased total cholesterol levels relative to wild-type controls
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• after 40 wks on a HFD, male homozygotes show significantly increased serum ALT levels relative to wild-type controls
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• after 40 wks on a HFD, male homozygotes show significantly increased serum AST levels relative to wild-type controls
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• after 28 wks on a HFD, both male and female homozygotes show increased energy expenditure, esp. during the active food-seeking period in the early dark phase
• however, the respiratory exchange ratio remains largely unaffected
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• female, but not male, homozygotes are protected from diet-induced obesity
• when fed a high-fat diet (HFD) starting at 10 wks of age, female homozygotes begin to gain less weight than wild-type controls, with the difference in body weight reaching statistical significance in the 18th wk of high-fat feeding
• after 30 wks on a HFD, the weight of female homozygotes is 11% lower than that of wild-type controls, largely due to a reduction in fat mass
• in contrast, male homozygotes fed a HFD show no differences in weight gain relative to wild-type controls
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• after 28 wks on a HFD, both male and female homozygotes show increased carbon dioxide production, esp. during the early phase of the dark period
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• after 28 wks on a HFD, both male and female homozygotes show increased oxygen consumption, esp. during the early phase of the dark period
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• after 26 wks on a HFD, male homozygotes show improved glucose disposal at 30 min after glucose challenge in an oral glucose tolerance test
• in contrast, female homozygotes show a glucose excursion curve similar to that in wild-type controls
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• after 40 wks on a HFD, male homozygotes show significantly increased free cholesterol and cholesteryl ester (CE) levels in the liver relative to wild-type controls
• in contrast, liver triacylglycerol (TAG), diacylglycerol (DAG), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and sphingomyelin (SM) levels remain normal
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adipose tissue
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• after 40 wks on a HFD, male, but not female, homozygotes show a slight decrease in BAT mass relative to wild-type controls
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• after 28 wks on a HFD, the whole body fat content in female homozygotes is 28% lower than that of wild-type controls
• however, the lean mass remains unaffected on a HFD
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• after 34 wks on a HFD, female homozygotes show a significant reduction in the weight of subcutaneous and perigonodonal/visceral fat depots relative to wild-type controls
• however, no lipodystrophy is observed
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liver/biliary system
• after 40 wks on a HFD, both male and female homozygotes show significantly increased liver weight relative to wild-type controls
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• after 40 wks on a HFD, male homozygotes show significantly increased free cholesterol and cholesteryl ester (CE) levels in the liver relative to wild-type controls
• in contrast, liver triacylglycerol (TAG), diacylglycerol (DAG), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and sphingomyelin (SM) levels remain normal
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behavior/neurological
N |
• on a HFD, homozygotes show normal food intake relative to age- and sex-matched wild-type controls
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• after 28 wks on a HFD, homozygotes appear more active than wild-type controls, with the difference being most prominent in the initial phase of the dark period and in female mice
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