Analysis Tools
mortality/aging
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• on a normal chow diet (ND), 60% of males die by 18 weeks of age
• on a high-fat diet (HFD), 60% of males die by 17 weeks of age
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• on a normal chow diet (ND), 1 of 16 males is found dead at 12 weeks of age, and 60% of males die by 18 weeks of age; a similar trend is observed on a high-fat diet (HFD) with 60% of males dead by 17 weeks of age
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growth/size/body
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• on a normal chow diet (ND), individually housed males show a normal body weight gain over a 15 week study period relative to wild-type controls
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• males exhibit significantly decreased total fat mass whether on NC or an HFD; the reduction is more pronounced on an HFD
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• although HFD-fed males are leaner than wild-type controls, their levels of lean mass are reduced by 30%
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• HFD-fed males show only a slight weight gain over a 15 week study period that is comparable to that observed on a ND, unlike HFD-fed wild-type males which increase their body weight by 160%
• however, no weight loss is observed whether on NC or an HFD
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behavior/neurological
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• males consume more chow whether on NC or an HFD
• HFD-fed males consume ~5 times more food per kg of body weight than similarly fed wild-type controls
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• when placed on an accelerated rotating horizontal rod, mice fall off the rod sooner than wild-type controls, indicating impaired motor coordination
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• in an open field test, males show a higher level of locomotor activity than wild-type controls at all time points examined; the total path length traveled is nearly double that of wild-type controls
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• all pups produced by mating female homozygotes with an ICR male die within 4 days due to maternal neglect
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• a subset of adult males exhibit seizures; one mouse had to be euthanized due to severe seizure events
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homeostasis/metabolism
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N |
• on a normal chow diet (ND), mice show only minimal differences in energy expenditure, oxygen consumption, and carbon dioxide production relative to wild-type controls
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• HFD-fed mice show significantly higher BUN levels than similarly fed wild-type controls
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• in an oral glucose tolerance test (OGTT), NC-fed males show normal glucose excursion rates but significantly lower fasting blood glucose levels than NC-fed wild-type controls
• HFD-fed males show increased glucose excursion rates and significantly lower fasting blood glucose levels than HFD-fed wild-type controls
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• at 8 weeks of age, fasted mice show a significant increase in both acylated and deacylated plasma ghrelin levels relative to wild-type controls
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• mice show severely reduced nonfasted plasma leptin levels whether on NC or an HFD
• HFD-fed mice secrete 13-fold less leptin than similarly fed wild-type controls
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• serum cholesterol levels are reduced by 20% on ND and by 60% on an HFD relative to those in similarly fed wild-type controls
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• serum HDL levels are reduced by 25% on ND and by 40% on an HFD relative to those in similarly fed wild-type controls
• however, VLDL and LDL levels are normal on both diets
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• serum triacylglyceride levels are only slightly reduced on ND but significantly reduced by 25% on an HFD relative to those in similarly fed wild-type controls
• following challenge with a bolus of olive oil in the presence of Pluronic F127 (an endothelial lipase inhibitor), mice show significantly lower blood triglyceride levels than similarly treated wild-type controls
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• HFD-fed mice show significantly higher energy expenditure than similarly fed wild-type controls
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• HFD-fed males show only a slight weight gain over a 15 week study period that is comparable to that observed on a ND, unlike HFD-fed wild-type males which increase their body weight by 160%
• however, no weight loss is observed whether on NC or an HFD
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• mRNA and protein levels of stearoyl-CoA desaturase 1 (SCD1) are severely reduced in the liver
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• HFD-fed mice show significantly higher serum alkaline phosphatase levels than similarly fed wild-type controls
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• HFD-fed mice show significantly low lactate dehydrogenase levels, unlike similarly fed wild-type controls
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• HFD-fed mice show significantly higher carbon dioxide production than similarly fed wild-type controls
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• HFD-fed mice show significantly higher oxygen consumption than similarly fed wild-type controls
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• HFD-fed males are resistant to becoming glucose-intolerant: at the end of an OGTT, HFD ending blood glucose levels return to levels seen before the initiation of the study, whereas glucose levels in HFD-fed wild-type males remain high
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• in an insulin tolerance test, HFD-fed males show higher insulin sensitivity than similarly fed wild-type controls, requiring glucose supplementation by 60 min
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• mice show significantly increased serum adiponectin levels whether on NC or an HFD
• HFD-fed mice secrete 9-fold more adiponectin per total fat mass than similarly fed wild-type controls
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• HFD-fed mice show reduced protein levels of bile acid synthetic enzymes (CYP8B1 and CYP27A1) in the liver relative to wild-type controls
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• in the small intestine, HFD-fed mice show a significantly larger and more hydrophobic bile acid pool than wild-type controls, with significantly higher levels of tauromuricholic acid (TMC), tauroursodeoxycholic acid (TUDC), taurocholic acid (TC), and taurodeoxycholic acid (TDC)
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• HFD-fed mice show a significant reduction in liver cholesterol (5-fold), LDL (5-fold) and HDL (6-fold) levels relative to similarly fed wild-type controls
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• HFD-fed mice show an 8-fold reduction of total FFA levels in the liver relative to similarly fed wild-type controls
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• mice show significantly decreased levels of oleic acid (18:DELTA19) whether on NC or an HFD
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• mice accumulate stearic acid (18:0) in the liver whether on NC or an HFD
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• mice accumulate arachidonic acid (20:0) in the liver whether on NC or an HFD
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• HFD-fed mice show a 8-fold reduction in liver triglyceride levels relative to similarly fed wild-type controls
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• HFD-fed mice show significantly higher metabolic rates than similarly fed wild-type controls
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adipose tissue
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• HFD-fed males show a significant reduction in brown fat mass and brown fat mass per g of body weight relative to similarly fed wild-type controls
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• males exhibit significantly decreased total fat mass whether on NC or an HFD; the reduction is more pronounced on an HFD
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• HFD-fed males show a 7.5-fold reduction in epididymal fat mass per gram of body weight relative to similarly fed wild-type controls
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• HFD-fed males show a significant reduction in inguinal fat mass per gram of body weight relative to similarly fed wild-type controls
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• HFD-fed males show a 3-fold reduction in mesenteric fat mass per gram of body weight relative to similarly fed wild-type controls
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• HFD-fed males show a significant reduction in retroperitoneal fat mass per gram of body weight relative to similarly fed wild-type controls
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liver/biliary system
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• HFD-fed mice show a significant reduction in liver cholesterol (5-fold), LDL (5-fold) and HDL (6-fold) levels relative to similarly fed wild-type controls
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• HFD-fed mice show an 8-fold reduction of total FFA levels in the liver relative to similarly fed wild-type controls
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• HFD-fed mice show a 8-fold reduction in liver triglyceride levels relative to similarly fed wild-type controls
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• HFD-fed mice show normal liver size and color with significantly reduced histological signs of hepatic steatosis and less inflammatory and fibrotic changes than similarly fed wild-type controls, indicating attenuation of NAFLD
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• HFD-fed mice show activation of the FXR and PPARalpha signaling pathways in the liver, likely contributing to a reduction in liver lipogenesis and reduced signs of NAFLD
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digestive/alimentary system
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• mice show significantly higher levels of fecal cholesterol, free fatty acids and total bile acids but lower levels of fecal triglycerides than wild-type controls
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• in the small intestine, HFD-fed mice show altered bile acid composition, an increase in the level of the intestinal FXR antagonist, tauromuricholic acid, and signs of attenuated FXR signaling
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nervous system
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• a subset of adult males exhibit seizures; one mouse had to be euthanized due to severe seizure events
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reproductive system
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• both male and female homozygotes are fertile
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