liver/biliary system
• mice fed a high-fat diet (HFD) for 12 weeks exhibit significantly lower hepatic cholesterol levels than diet-matched control mice
• however, hepatic cholesterol levels are relatively normal under standard-fat diet (SFD) conditions
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• HFD-fed mice exhibit significantly lower hepatic TG levels than diet-matched control mice
• however, hepatic TG levels are normal under SFD conditions
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• HFD-fed mice exhibit a significantly lower liver weight to body weight ratio (LW/BW) than diet-matched controls
• however, LW/BW ratio is normal under SFD conditions
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• mice fed a HFD for 12 weeks show significantly less hepatic steatosis than diet-matched controls, as determined by liver macroscopic appearance, H&E staining, Oil Red O staining, LW/BW ratio, and hepatic lipid contents
• administration of Ad-shRNA targeting INSIG1 (insulin induced gene 1, a direct target of Mir32) abrogates the alleviation of hepatic steatosis, insulin resistance, hyperlipidemia, and overexpression of lipogenic genes in HFD-fed mice
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• HFD-fed mice show activation of AKT signaling in the liver while mRNA and protein levels of hepatic genes involved in fatty acyl-CoA, triglyceride, and cholesterol biosynthesis are markedly reduced
• HFD-fed mice show significantly alleviated hepatic endoplasmic reticulum stress relative to diet-matched control mice
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homeostasis/metabolism
N |
• mice exhibit normal oxygen consumption, carbon dioxide production, respiratory exchange rate (RER), and heat generation regardless of whether they are fed a HFD or SFD
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• HFD-fed mice exhibit significantly lower total serum cholesterol levels than diet-matched control mice
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• HFD-fed mice exhibit significantly lower serum LDL cholesterol levels than diet-matched control mice
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• HFD-fed mice exhibit significantly lower serum ALT levels than diet-matched control mice
• however, serum ALT levels are relatively normal under SFD conditions
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• HFD-fed mice exhibit significantly lower serum AST levels than diet-matched control mice
• however, serum AST levels are not significantly altered under SFD conditions
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• HFD-fed mice show improved glucose tolerance relative to diet-matched control mice, as indicated by an intraperitoneal glucose tolerance test (IPGTT)
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• HFD-fed mice show enhanced insulin sensitivity relative to diet-matched control mice, as indicated by an insulin tolerance test (IPITT
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• mice fed a high-fat diet (HFD) for 12 weeks exhibit significantly lower hepatic cholesterol levels than diet-matched control mice
• however, hepatic cholesterol levels are relatively normal under standard-fat diet (SFD) conditions
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• HFD-fed mice exhibit significantly lower hepatic TG levels than diet-matched control mice
• however, hepatic TG levels are normal under SFD conditions
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• lipidomic analysis of livers from HFD-fed mice showed a significant reduction in triglyceride and cholesterol ester species relative to diet-matched controls; specifically, TG_48:1, TG_48:2, TG_48:3, TG_49:1, TG_50:1, TG_50:2, TG_50:3, TG_52:1, TG_54:2, CE_22:6, and CE_18:2 are dramatically reduced
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cellular
• HFD-fed mice show significantly alleviated hepatic endoplasmic reticulum stress relative to diet-matched control mice
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growth/size/body
N |
• mice exhibit normal body weight regardless of whether they are fed a HFD or SFD
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behavior/neurological
N |
• mice exhibit normal food intake and total activity regardless of whether they are fed a HFD or SFD
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