growth/size/body
• mice fed a high-fat diet (HFD) for 12 weeks exhibit a significantly lower body weight than HFD-fed control mice
• however, body weight is normal under normal chow diet (NCD) conditions
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homeostasis/metabolism
• livers from HFD-fed mice exhibit a significantly higher number of autophagic structures (autophagosomes/autolysosomes) than livers from diet-matched controls
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• most of the increased LC3 puncta in FFA-treated hepatocytes colocalize with MitoTracker (a mitochondrial-specific dye), indicating enhanced mitophagy; PINK1 (a marker protein of mitophagy) is increased in the liver
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• liver lysates from HFD-fed mice show increased expression of autophagosome proteins MAP1LC3A (LC3), ULK1 and SQSTM1 (p62)
• primary hepatocytes transfected with GFP-LC3 have more LC3 puncta per cell than control hepatocytes
• lysates from primary hepatocytes treated with bafilomycin A1 (BafA1) show significantly more LC3 than BafA1-treated control hepatocytes
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• HFD-fed mice exhibit significantly lower blood glucose levels than diet-matched controls
• however, blood glucose levels are normal under NCD conditions
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• HFD-fed mice exhibit significantly lower serum insulin levels than diet-matched controls
• however, serum insulin levels are normal under NCD conditions
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• HFD-fed mice exhibit significantly lower serum cholesterol levels than diet-matched controls
• however, serum cholesterol levels are normal under NCD conditions
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• HFD-fed mice exhibit significantly lower serum FFA levels than diet-matched controls
• however, serum FFA levels are normal under NCD conditions
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• HFD-fed mice exhibit significantly lower serum TG levels than diet-matched controls
• however, serum TG levels are normal under NCD conditions
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• HFD-fed mice exhibit significantly lower serum ALT levels than diet-matched controls
• however, serum ALT levels are normal under NCD conditions
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• HFD-fed mice exhibit significantly lower serum AST levels than diet-matched controls
• however, serum AST levels are normal under NCD conditions
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• HFD-fed mice show a significantly higher energy expenditure than diet-matched controls
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• primary hepatocytes from HFD-fed mice show an improved oxygen consumption rate
• HFD-fed mice show a significantly higher oxygen consumption rate (VO2) during day and night
• however, no changes in locomotor activity or food intake are noted under HFD conditions
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• HFD-fed mice exhibit improved glucose tolerance relative to diet-matched controls
• however, glucose tolerance is normal under NCD conditions
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• however, insulin tolerance is normal under NCD conditions
• HFD-fed mice exhibit improved insulin sensitivity relative to diet-matched controls
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• mice fed a HFD or a MCD diet exhibit significantly lower liver cholesterol levels than diet-matched controls
• however, liver cholesterol levels are normal under NCD conditions
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• mice fed a HFD or a MCD diet exhibit significantly lower liver triglyceride levels than diet-matched controls
• however, liver triglyceride levels are normal under NCD conditions
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liver/biliary system
• HFD-fed mice exhibit a significantly higher mtDNA level in the liver than diet-matched controls
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• mice fed a HFD or a MCD diet exhibit significantly lower liver cholesterol levels than diet-matched controls
• however, liver cholesterol levels are normal under NCD conditions
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• mice fed a HFD or a MCD diet exhibit significantly lower liver triglyceride levels than diet-matched controls
• however, liver triglyceride levels are normal under NCD conditions
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• mice fed a HFD for 12 weeks exhibit attenuated hepatic steatosis, as indicated by a darker liver color and a significant reduction in liver size, liver weight, hepatic triglyceride and cholesterol level, nonalcoholic fatty liver disease (NAFLD) activity score (NAS), and fibrosis score relative to HFD-fed control mice
• mice fed a methionine/choline-deficient (MCD) diet for 4 weeks also show reduced hepatic steatosis with darker liver color and significantly lower hepatic triglyceride and cholesterol levels, NAS and fibrosis scores than MCD-fed control mice
• however, mice show no differences in liver size, weight or lipid accumulation when fed a normal chow diet (NCD)
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• following insulin administration, both HFD-fed and NCD-fed mice show increased phosphorylation of the Ser473 residue of AKT in the liver relative to controls
• however, expression of fatty acid beta-oxidation- and lipogenesis-related genes is not significantly altered
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• primary hepatocytes from HFD-fed mice show a significant increase in the extracellular acidification rate (ECAR)
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cellular
• HFD-fed mice exhibit a significantly higher mtDNA level in the liver than diet-matched controls
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• HFD-fed mice exhibit a significantly higher cristae volume density in the liver than diet-matched controls
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• HFD-fed mice exhibit a significantly greater area of mitochondria in the liver than diet-matched controls
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• livers from HFD-fed mice exhibit a significantly higher number of autophagic structures (autophagosomes/autolysosomes) than livers from diet-matched controls
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• most of the increased LC3 puncta in FFA-treated hepatocytes colocalize with MitoTracker (a mitochondrial-specific dye), indicating enhanced mitophagy; PINK1 (a marker protein of mitophagy) is increased in the liver
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• liver lysates from HFD-fed mice show increased expression of autophagosome proteins MAP1LC3A (LC3), ULK1 and SQSTM1 (p62)
• primary hepatocytes transfected with GFP-LC3 have more LC3 puncta per cell than control hepatocytes
• lysates from primary hepatocytes treated with bafilomycin A1 (BafA1) show significantly more LC3 than BafA1-treated control hepatocytes
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• HFD-fed mice show significantly higher levels of mitochondrial respiratory chain complex proteins, such as succinate dehydrogenase complex iron sulfur subunit B (SDHB), cytochrome b-c1 complex subunit 2 (UQCR2), and ATP synthase subunit alpha (ATP5A) in the liver than diet-matched controls
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• primary hepatocytes from HFD-fed mice show a significant increase in ATP production
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