Analysis Tools
growth/size/body
 N |
• under steady state conditions, young male mice (1- to 2-month-old) exhibit normal body weight relative to wild-type controls
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• after 8-12 weeks on a high-fat diet (HFD), male mice exhibit a lower body weight than HFD-fed wild-type controls
• however, after a diet switch from HFD to CD, body weight returns to the level of mice kept on CD
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• when placed on a control diet (CD), male mice gain less weight over time than diet-matched wild-type controls
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liver/biliary system
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N |
• under steady state conditions, young male mice (1- to 2-month-old) exhibit no differences in liver weight or histology relative to wild-type controls
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• aged (12- to 15-month-old) males exhibit dilated liver sinusoids
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• HFD-fed males show increased liver apoptosis, as confirmed by immunoblotting against cleaved caspase 3
• however, neither transcriptome nor protein expression analysis showed a lipid-driven ER stress response in the liver, despite increased apoptosis
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• aged (12- to 15-month-old) males exhibit abundant vacuoles in hepatocytes
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• HFD-fed, but not CD-fed, male mice exhibit a lower liver weight than HFD-fed wild-type controls
• however, after a diet switch from HFD to CD, liver weight returns to the level of mice kept on CD
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• HFD-fed males exhibit a lower body and liver weight and a significant reduction in total lipid, diacylglycerol (DAG), and triacylglycerol (TAG) content than HFD-fed wild-type controls
• however, after a diet switch from HFD to CD, liver weight, total lipid, DAG and TAG content as well as ORO and PAS signals return to baseline levels
• HFD-fed males show no significant changes in fibrosis, liver function or serum alanine aminotransferase (ALT) levels relative to HFD-fed wild-type controls
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• 2 days after a single i.p. injection of ER stressor tunicamycin (1 mg/kg), livers show a significant increase in total lipid, DAG and TAG content along with increased cholesterol ester (CE) abundance and decreased PAS staining relative to wild-type controls
• tunicamycin-challenged livers show perturbed induction of the unfolded protein response (UPR), leading to dysregulated lipid homeostasis and exacerbated development of NAFLD
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• aged (12- to 15-month-old) males accumulate more free fatty acids (FFA), DAG, cholesterol, and cholesteryl esters in liver than wild-type control males while liver TAG remains similar to wild-type levels; histology showed increased lipid accumulation with dilated sinusoids, abundant vacuoles in hepatocytes, and increased signal after ORO staining
• in contrast, aged females are protected from developing a hepatosteatosis phenotype
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homeostasis/metabolism
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• after 8 weeks on a HFD male mice develop insulin resistance, as measured by HOMA- IR
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• HFD-fed males show significantly higher ceramide levels in the liver than HFD-fed wild-type controls
• however, after a HFD to CD switch, liver ceramide levels drop to levels comparable to those in mice kept on CD
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cellular
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• HFD-fed males show increased liver apoptosis, as confirmed by immunoblotting against cleaved caspase 3
• however, neither transcriptome nor protein expression analysis showed a lipid-driven ER stress response in the liver, despite increased apoptosis
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• after ER-stress induction by tunicamycin, mice exhibit exacerbated ER stress in the liver, as indicated by increased HSPA5 (heat shock protein 5) expression and consequently augmented liver lipid storage
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cardiovascular system
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• aged (12- to 15-month-old) males exhibit dilated liver sinusoids
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