Analysis Tools
growth/size/body
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• after 12 weeks of high-fat diet (HFD) feeding, both male and female mice show no significant differences in weight gain, % lean mass or % fat mass relative to HFD-fed wild-type controls
• HFD-fed females show no detectable changes in wet tissue mass (normalized to body mass) relative to HFD-fed wild-type controls, as determined in liver, lung, heart, brain, fat and muscle tissue
• chow-fed females show normal weight gain, body composition, and body length
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• after 12 weeks of HFD feeding, females show significantly shorter body lengths than HFD-fed wild-type females
• however, HFD-fed males exhibit no significant changes in body length
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homeostasis/metabolism
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• during an oral glucose tolerance test (OGTT), both HFD-fed male and female mice show no significant differences in fasting blood glucose, fasting plasma insulin, or serum insulin levels at 30 min and 60 min after the glucose bolus relative to HFD-fed wild-type controls
• moreover, chow-fed females show normal fasting levels of glucose and insulin, indicating normal whole-body glucose homeostasis
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• after 12 weeks of HFD feeding, female mice exhibit diet-induced dyslipidemia with significantly higher plasma triglyceride, free fatty acid and cholesterol levels and altered VLDL and HDL properties relative to HFD-fed wild-type females
• HFD-fed females show a modest increase in plasma hexosylceramide levels, including glucosylceramide (GlcCer) and galactosylceramide (GalCer), along with a dramatic reduction in plasma eicosanoid, bile acid, and fatty acid (FA) conjugate species
• in contrast, HFD-fed male mice show no major alterations in plasma lipid levels
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• HFD-fed females, but not males, exhibit significantly higher plasma cholesterol levels
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• HFD-fed females carry most of their cholesterol in smaller sized HDL particles
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• HFD-fed females, but not males, exhibit significantly higher plasma free fatty acid levels
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• HFD-fed females, but not males, exhibit significantly higher plasma triglyceride levels
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• HFD-fed females carry most of their triglycerides in smaller sized VLDL particles
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• HFD-fed females exhibit a negative energy balance during light hours relative to HFD-fed wild-type females
• however, HFD-fed females show normal average daily (sum of light and dark hours) energy expenditure
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• HFD-fed females show a marked increase in the mRNA expression of Lipf (lipase, gastric) and Pla2g5 (phospholipase A2, group V) along with a 571-fold upregulation of Gpr50 (G-protein-coupled receptor 50) in visceral fat
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• HFD-fed females exhibit a dramatic reduction in plasma bile acid levels
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• HFD-fed females show a significant increase in the abundance of monounsaturated vs saturated species of one cholesterol ester (CE) species, as indicated by a higher 18:1w7/18:0 ratio, as well as a higher total amount of CE 18:1w9 in liver
• however, total amounts of hepatic cholesterol, cholesterol esters, and unesterified cholesterol are relatively unaffected
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• HFD-fed females show significantly lower levels of the FFA species 16:0 and 18:1w9 in liver
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• HFD-fed females show a significant increase in the abundance of monounsaturated vs saturated species of two phospholipids (PL) species, as indicated by higher16:1/16:0 and 18:1w7/18:0 ratios in liver
• however, total amounts of hepatic phospholipids (PL) and ceramides are relatively unaffected
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• HFD-fed females show a modest increase in plasma phosphatidylcholine (PC) levels
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• HFD-fed females exhibit a modest increase in plasma hexosylceramide levels, including glucosylceramide (GlcCer) and galactosylceramide (GalCer)
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• HFD-fed females show a significant increase in the abundance of monounsaturated vs saturated species of several TG species, as indicated by higher 16:1/16:0, 18:1w7/18:0 and 18:1w9/18:0 ratios in liver
• however, total amounts of hepatic triglycerides are relatively unaffected
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• after 12 weeks of HFD feeding, female mice show alterations in the size and lipid content of both very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL)
• moreover, HFD-fed females show marked changes in the plasma lipidome, visceral fat transcriptome, and hepatic lipid metabolism
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liver/biliary system
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• HFD-fed females show a significant increase in the abundance of monounsaturated vs saturated species of one cholesterol ester (CE) species, as indicated by a higher 18:1w7/18:0 ratio, as well as a higher total amount of CE 18:1w9 in liver
• however, total amounts of hepatic cholesterol, cholesterol esters, and unesterified cholesterol are relatively unaffected
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• HFD-fed females show significantly lower levels of the FFA species 16:0 and 18:1w9 in liver
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• HFD-fed females show a significant increase in the abundance of monounsaturated vs saturated species of several TG species, as indicated by higher 16:1/16:0, 18:1w7/18:0 and 18:1w9/18:0 ratios in liver
• however, total amounts of hepatic triglycerides are relatively unaffected
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• despite normal total amounts of cholesterol and triglycerides in the liver, HFD-fed females show a significant increase in the average diameter of Oil Red O-positive lipid droplets in liver sections with an Oil Red O staining score of 2 (= multi-focal and coalescing staining)
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• HFD-fed females exhibit alterations in liver insulin signaling and hepatic insulin resistance with no perturbations in wholebody glucose homeostasis
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behavior/neurological
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• HFD-fed females exhibit no significant changes in daily (sum of light and dark hours) activity relative to HFD-fed wild-type females
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• HFD-fed females exhibit significantly lower food intake during light hours than HFD-fed wild-type females
• however, HFD-fed females show normal average daily (sum of light and dark hours) food intake
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