growth/size/body
N |
• mice exhibit normal body weight under fed or fasted conditions
• mice fed a high-fat diet for 12 weeks show no difference in body weight gain from controls and no differences in gonadal white adipose tissue, inguinal white adipose tissue, or liver weights
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• mice lose body weight after 7 days of ketogenic diet feeding, however kidney and liver weights are normal on a ketogenic diet
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• female, but not male, mice show an increase in kidney weight when fed a high-fat diet
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homeostasis/metabolism
• mice exhibit acceleration of hepatic ketogenesis
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• glucose-invoked insulin production is improved in high-fat diet-fed males
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• mice exhibit suppression of both fed and fasted blood glucose levels, however this small suppression in blood glucose is not likely physiologically significant
• males fed a high-fat diet exhibit a suppression in blood glucose, however triglycerides, cholesterol, and nonesterified fatty acids are unaffected
• fasting high-fat diet-fed males and females exhibit suppression in blood glucose levels
• mice fed a ketogenic diet exhibit a large suppression in blood glucose
• in summary, mice tolerate a 24 hour fast and high-fat diet feeding with normal and improved homeostasis, respectively, but are unable to sustain glucose homeostasis under a ketogenic diet
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• mice exhibit suppression fasted blood glucose levels, however this small suppression in blood glucose is not likely physiologically significant
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hypoglycemia
(
J:332296
)
• mice fed a ketogenic diet for 1 week become severely hypoglycemic
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• ketone body beta-hydroxybutyrate (BHB) is increased in fed mice but not fasted mice, indicating enhanced ketogenesis
• BHB concentrations are increased in high-fat diet-fed males
• fasting BHB level is increased in high-fat diet-fed males and females without affecting triglyceride or cholesterol concentrations
• males, but not females, fed a ketogenic diet show increased circulating BHB level
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• mice exhibit an increase in circulating lactate
• fasting high-fat diet-fed males and females exhibit an increase in blood lactate concentration
• mice fed a ketogenic diet show an exacerbated increase in circulating lactate than under basal conditions
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• fasting nonesterified fatty acid (NEFA) level is increased in high-fat diet-fed males and females without affecting triglyceride or cholesterol concentrations
• however, chow-fed mice exhibit normal circulating NEFA and triglyceride levels
• males and females fed a ketogenic diet show increased circulating NEFA levels
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• males fed a ketogenic diet show increased circulating triglycerides
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• primary hepatocytes show decreased production of glucose from labeled lactate or glutamine indicating suppressed gluconeogenesis
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• high-fat diet-fed males show improved blood glucose tolerance with increased glucose clearance and lower insulin levels indicating protection from high-fat-induced glucose tolerance
• female high-fat diet-fed mice do not exhibit changes in glucose or insulin tolerance
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• insulin tolerance test shows an improvement in insulin-stimulated blood glucose clearance in high-fat diet-fed males
• female high-fat diet-fed mice do not exhibit changes in insulin tolerance
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• liver triglyceride content is increased following a 24 hour fast
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• 24 hour fasted males show an increase in liver metabolites, especially urea cycle intermediates including arginiosuccinate, citrulline, and homocitrulline
• almost all N-acetylated forms of free amino acids are elevated in the liver
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endocrine/exocrine glands
• glucose-invoked insulin production is improved in high-fat diet-fed males
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cellular
• fed and fasted mice show an increased abundance of lysine-acetylated mitochondrial proteins in the liver, indicating mitochondrial protein hyperacetylation in liver
• mice fed a high-fat diet exhibit a large increase in the abundance of lysine-acetylated proteins
• however, ketogenic diet-fed mice exhibit a similar pattern of lysine-acetylated proteins as controls
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• mice exhibit acceleration of hepatic ketogenesis
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liver/biliary system
• liver triglyceride content is increased following a 24 hour fast
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• livers of males fed a ketogenic diet are lipid laden with abundant lipid droplet deposition
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• 24 hour fasted males show an increase in liver metabolites, especially urea cycle intermediates including arginiosuccinate, citrulline, homocitrulline, and urea
• almost all N-acetylated forms of free amino acids are elevated in the liver
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renal/urinary system
• female, but not male, mice show an increase in kidney weight when fed a high-fat diet
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