Impaired energy homeostasis in C/EBP alpha knockout mice.
Mice homozygous for the targeted deletion of the c/ebp alpha gene, which expresses the CCAAT/enhancer-binding protein alpha (C/EBP alpha), did not store hepatic glycogen and died from hypoglycemia within 8 hours after birth. In these mutant mice, the amounts of glycogen synthase messenger RNA were 50 to 70 percent of normal and the transcriptional induction of the genes for two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, was delayed. The hepatocytes and adipocytes of the mutant mice failed to accumulate lipid and the expression of the gene for uncoupling protein, the defining marker of brown adipose tissue, was reduced. This study demonstrates that C/EBP alpha is critical for the establishment and maintenance of energy homeostasis in neonates.
Wang
N D
ND
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Finegold
M J
MJ
Bradley
A
A
Ou
C N
CN
Abdelsayed
S V
SV
Wilde
M D
MD
Taylor
L R
LR
Wilson
D R
DR
Darlington
G J
GJ
D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D005786:Gene Expression Regulation; D005952:Glucose-6-Phosphatase / Q000235:genetics; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007473:Ion Channels; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000235:genetics; D000071256:Uncoupling Protein 1
D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007473:Ion Channels; D008112:Liver Glycogen; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012709:Serum Albumin; D000071256:Uncoupling Protein 1; D006006:Glycogen Synthase; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)