Analysis Tools
growth/size/body
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• at 36 wks of age, chow-fed male homozygotes show a ~8% decrease in lean mass as a % of total body weight relative to wild-type controls
• however, no differences are observed in lean mass between HFD-fed homozygotes and wild-type controls
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• on a standard chow diet, male homozygotes gain significantly more body weight than wild-type controls
• on a standard chow diet, female homozygotes also gain more body weight than wild-type controls; however, body weight differences become apparent only at ~9 mo of age
• surprisingly, on a high-fat diet (HFD), male and female homozygotes gain weight at a rate similar to that in wild-type controls
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behavior/neurological
| N |
• chow-fed homozygotes display normal ambulatory (horizontal plane movements) and total physical activity levels relative to wild-type controls
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• chow-fed homozygotes consume more food during the second half of the dark phase of the photocycle relative to chow-fed wild-type controls; however, total food intake is normal in the light phase
• on a standard chow diet, average meal size over a 24-h period is 0.21 +/- 0.016 g versus 0.14 +/- 0.002 g for wild-type controls; during the dark phase, average meal size is 0.26 +/- 0.04 g versus 0.16 +/- 0.007 g for wild-type controls
• chow-fed homozygotes show a decreased satiety ratio, defined as intermeal interval (time between consecutive meals) divided by meal size (min/g), during the dark phase of the photocycle; however, meal number and intermeal interval remain normal over a 24-h period relative to wild-type controls
• on a HFD diet, homozygotes show normal food intake, meal size, meal number and satiety ratio relative to wild-type controls
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homeostasis/metabolism
| N |
• at 35 wks of age, chow-fed homozygotes show no differences in oxygen consumption, carbon dioxide production, energy expenditure, and respiratory exchange ratio (RER) relative to wild-type controls
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• chow-fed homozygotes show increased insulin secretion in response to glucose challenge
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• chow-fed homozygotes show a 2-fold increase in fasting (7-h) serum insulin levels relative to wild-type controls
• in contrast, fasting glucose levels remain normal
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• chow-fed homozygotes show a 3-fold increase in serum leptin levels relative to wild-type controls
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• chow-fed homozygotes show a 2-fold increase in serum resistin levels relative to wild-type controls
• however, serum levels of other adipokines, including adiponectin, MCP-1, IL-6, and TNF, are not significantly altered
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• an insulin tolerance test (ITT) confirmed reduced glucose clearance rates in peripheral tissues in response to insulin, resulting in higher blood glucose levels during the test
• chow-fed homozygotes display insulin resistance, as revealed by a ~2-fold increase in the HOMA-IR (homeostatic model assessment of insulin resistance) index, and much higher serum insulin levels in a glucose tolerance test (GTT) test
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• chow-fed homozygotes display a ~50% increase in hepatic triglycerol (TG) content relative to wild-type controls
• however, liver weight and serum TG levels are not significantly increased
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liver/biliary system
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• chow-fed homozygotes display a ~50% increase in hepatic triglycerol (TG) content relative to wild-type controls
• however, liver weight and serum TG levels are not significantly increased
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• at 48 wks of age, chow-fed homozygotes display marked accumulation of lipid droplets in the liver relative to wild-type controls
• hepatic expression of lipid synthesis genes is increased
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• chow-fed homozygotes subjected to a 7-hr fast followed by insulin injection show impaired hepatic insulin signaling, as revealed by a smaller increase (1.3-fold) in insulin-induced Akt phosphorylation in mutant livers relative to a 5-fold increase in wild-type livers
• in contrast, insulin signaling is largely normal in mutant adipose tissue and skeletal muscles
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muscle
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• chow-fed homozygotes display reduced skeletal muscle mitochondrial content, as judged by the expression levels of mitochondria-specific markers
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• chow-fed homozygotes display reduced skeletal muscle AMPK activation and mitochondrial biogenesis
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adipose tissue
| N |
• at 48 wks of age, chow-fed homozygotes display normal adipocyte cell size in epididymal fat depots relative to wild-type controls
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• at 36 wks of age, chow-fed male homozygotes show a ~10% increase in fat mass as a % of total body weight relative to wild-type controls
• however, no differences are observed in fat mass between HFD-fed homozygotes and wild-type controls
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endocrine/exocrine glands
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• chow-fed homozygotes show increased insulin secretion in response to glucose challenge
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nervous system
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• on a standard chow diet, homozygotes show increased hypothalamic expression of two orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AGRP), while expression of anorexigenic neuropeptides remains relatively normal
• on a HFD diet, hypothalamic appetite-regulating gene expression is similar to that in wild-type controls
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