All Phenotypes Pcx<tm1c(EUCOMM)Wtsi> MGI Mouse

growth/size/body region phenotype ( J:332296 )

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

increased susceptibility to weight loss ( J:332296 )

• mice lose body weight after 7 days of ketogenic diet feeding, however kidney and liver weights are normal on a ketogenic diet

increased kidney weight ( J:332296 )

• female, but not male, mice show an increase in kidney weight when fed a high-fat diet

abnormal fatty acid oxidation ( J:332296 )

• mice exhibit acceleration of hepatic ketogenesis

abnormal insulin secretion ( J:332296 )

• glucose-invoked insulin production is improved in high-fat diet-fed males

decreased circulating glucose level ( J:332296 )

• 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

decreased fasting circulating glucose level ( J:332296 )

• mice exhibit suppression fasted blood glucose levels, however this small suppression in blood glucose is not likely physiologically significant

hypoglycemia ( J:332296 )

• mice fed a ketogenic diet for 1 week become severely hypoglycemic

increased circulating ketone body level ( J:332296 )

• 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

increased circulating lactate level ( J:332296 )

• 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

increased circulating free fatty acids level ( J:332296 )

• 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

increased circulating triglyceride level ( J:332296 )

• males fed a ketogenic diet show increased circulating triglycerides

impaired gluconeogenesis ( J:332296 )

• primary hepatocytes show decreased production of glucose from labeled lactate or glutamine indicating suppressed gluconeogenesis

improved glucose tolerance ( J:332296 )

• 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

abnormal insulin clearance ( J:332296 )

• 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

increased liver triglyceride level ( J:332296 )

• liver triglyceride content is increased following a 24 hour fast

abnormal amino acid metabolism ( J:332296 )

• 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

abnormal insulin secretion ( J:332296 )

• glucose-invoked insulin production is improved in high-fat diet-fed males

abnormal mitochondrial physiology ( J:332296 )

• 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

abnormal fatty acid oxidation ( J:332296 )

• mice exhibit acceleration of hepatic ketogenesis

increased liver triglyceride level ( J:332296 )

• liver triglyceride content is increased following a 24 hour fast

hepatic steatosis ( J:332296 )

• livers of males fed a ketogenic diet are lipid laden with abundant lipid droplet deposition

abnormal liver physiology ( J:332296 )

• 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

increased kidney weight ( J:332296 )

• female, but not male, mice show an increase in kidney weight when fed a high-fat diet

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

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