Impaired Energy Homeostasis in C/EBPα Knockout Mice

• Published in: Science (American Association for the Advancement of Science) 1995-08, Vol.269 (5227), p.1108-1112
• Main Authors: NAI-DY WANG, FINEGOLD, M. J, BRADLEY, A, OU, C. N, ABDELSAYED, S. V, WILDE, M. D, TAYLOR, L. R, WILSON, D. R, DARLINGTON, G. J
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adipose Tissue, Brown - metabolism; Animals; Animals, Newborn; Bioenergetics; Biological and medical sciences; Blood Glucose - metabolism; Boreal forests; Carrier Proteins - genetics; CCAAT-Enhancer-Binding Proteins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Energy Metabolism; Female; Food supply; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genetic aspects; Glucose-6-Phosphatase - genetics; Glycogen Synthase - genetics; Glycogen Synthase - metabolism; Hares; Histology; Homeostasis; Humans; Intermediate and energetic metabolism; Ion Channels; Lipid Metabolism; Liver - metabolism; Liver Glycogen - metabolism; Male; Marine fishes; Membrane Proteins - genetics; Metabolisms and neurohumoral controls; Mice; Mice, Knockout; Mitochondrial Proteins; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Phosphoenolpyruvate Carboxykinase (GTP) - genetics; Population dynamics; Predation; Predators; RNA, Messenger - metabolism; Serum Albumin - genetics; Uncoupling Protein 1; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7652557

Mice homozygous for the targeted deletion of the c/ebpα gene, which expresses the CCAAT/enhancer-binding protein α (C/EBPα), 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/EBPα is critical for the establishment and maintenance of energy homeostasis in neonates.