homeostasis/metabolism
• when fed a high fat diet (HFD) at 4 weeks of age for 16 weeks, males show significantly lower blood glucose levels than wild-type controls at both fed and fasting conditions
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• on regular chow, 4-mo-old males exhibit significantly lower fasting blood glucose levels than wild-type controls
• when fed a HFD at 4 weeks of age for 16 weeks, males show significantly lower fasting blood glucose levels than similarly treated wild-type controls
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• HFD-fed males show significantly lower fasting plasma insulin levels than HFD-fed wild-type controls
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• after 16-weeks on a HFD, males show a significant reduction of total plasma cholesterol levels relative to similarly fed wild-type controls
• in contrast, circulating triglyceride and free fatty acid levels are not significantly altered
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• after 16-weeks on a HFD, males show a trend towards a higher oxygen consumption rate than HFD-fed wild-type controls
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• after 16-weeks on a HFD, males show a significantly lower respiratory exchange ratio during the dark cycle than HFD-fed wild-type controls
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• on regular chow, males display significantly lower blood glucose levels and reduced area under the curve (AUC) in a pyruvate tolerance test (PTT), suggesting attenuated hepatic gluconeogenesis
• on regular chow, both hepatic mRNA levels and hepatic activity of G6Pase (glucose-6-phosphatase) are significantly reduced, whereas hepatic PEPCK (phosphoenolpyruvate carboxykinase) and FoxO1 mRNA levels remain normal
• in culture, primary hepatocytes show significantly reduced glucose production in response to glucagon (via cAMP) stimulation
• HFD-fed males show significantly lower blood glucose levels and reduced AUC in a PTT test and a small but significant reduction in hepatic glucose 6-phosphate levels
• after HFD feeding, hepatic G6Pase mRNA levels show a 2-fold reduction, whereas hepatic PEPCK mRNA levels are reduced to a lesser extent
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• on regular chow, males show significantly improved blood glucose profiles and reduced AUC in a glucose tolerance test
• when fed a HFD at 4 weeks of age for 16 weeks, males show enhanced glucose tolerance, unlike similarly fed wild-type controls
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• HFD-fed males show significantly lower blood glucose levels and reduced AUC in an insulin tolerance test, and a significantly lower insulin resistance index (HOMA-IR) than HFD-fed wild-type controls
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• HFD-fed males show significantly lower hepatic triglyceride content than HFD-fed wild-type controls
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• on regular chow, G6Pase (glucose-6-phosphatase) activity is significantly reduced in the liver
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growth/size/body
• when fed a HFD at 4 weeks of age for 16 weeks, males become obese but gain 5-10% less weight than similarly fed wild-type controls
• however, fat mass and lean mass (normalized to body weight) are not significantly altered
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liver/biliary system
• HFD-fed males show a significantly lower Kupffer cell content in the liver than HFD-fed wild-type controls
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• HFD-fed males show significantly lower hepatic triglyceride content than HFD-fed wild-type controls
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• after 16 weeks on a HFD, males exhibit significantly lower hepatic fat deposition than HFD-fed wild-type controls, as shown by oil red O staining
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immune system
• HFD-fed males show a significantly lower Kupffer cell content in the liver than HFD-fed wild-type controls
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• HFD-fed males show significantly reduced macrophage infiltration into liver tissue, as shown by a decreased Kupffer cell content, reduced % of F4/80 positive cells, and lower hepatic expression of the C-C chemokine receptor 2 (CCR2) and CD68
• HFD-fed males show significantly reduced macrophage infiltration into adipose tissue, as shown by a reduced % of F4/80 positive cells, smaller adipocyte size, and lower CCR2 mRNA levels along with decreased F4/80 and CD68 mRNA levels in stromal vascular cells from epididymal adipose tissue
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behavior/neurological
• when fed a HFD at 4 weeks of age for 16 weeks, males show a small decrease in food intake, consistent with less weight gain, relative to similarly fed wild-type controls
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hematopoietic system
• HFD-fed males show a significantly lower Kupffer cell content in the liver than HFD-fed wild-type controls
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• HFD-fed males show significantly reduced macrophage infiltration into liver tissue, as shown by a decreased Kupffer cell content, reduced % of F4/80 positive cells, and lower hepatic expression of the C-C chemokine receptor 2 (CCR2) and CD68
• HFD-fed males show significantly reduced macrophage infiltration into adipose tissue, as shown by a reduced % of F4/80 positive cells, smaller adipocyte size, and lower CCR2 mRNA levels along with decreased F4/80 and CD68 mRNA levels in stromal vascular cells from epididymal adipose tissue
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adipose tissue
• HFD-fed males show significantly smaller adipocytes in epididymal adipose tissues relative to HFD-fed wild-type controls
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cellular
• HFD-fed males show significantly reduced macrophage infiltration into liver tissue, as shown by a decreased Kupffer cell content, reduced % of F4/80 positive cells, and lower hepatic expression of the C-C chemokine receptor 2 (CCR2) and CD68
• HFD-fed males show significantly reduced macrophage infiltration into adipose tissue, as shown by a reduced % of F4/80 positive cells, smaller adipocyte size, and lower CCR2 mRNA levels along with decreased F4/80 and CD68 mRNA levels in stromal vascular cells from epididymal adipose tissue
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cardiovascular system
• HFD-fed males show a significantly lower Kupffer cell content in the liver than HFD-fed wild-type controls
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