Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta are protected against diet-induced obesity.
The CCAAT/enhancer-binding protein beta (C/EBPbeta) is required for adipocyte differentiation and maturation. We have studied the role of the transcription factor, C/EBPbeta, in the development of diet-induced obesity. Mice with a deletion in the gene for C/EBPbeta (C/EBPbeta(-/-)) and wild-type mice were fed a high-fat diet (60% fat) for 12 weeks. The C/EBPbeta(-/-) mice lost body fat, whereas the wild-type mice increased their total body fat on a high-fat diet. The C/EBPbeta(-/-) mice had lower levels of blood triglycerides, free fatty acids, cholesterol, and hepatic triglyceride accumulation compared with the wild-type mice, thus protecting them from diet-induced obesity and fatty liver on a high-fat diet. Deletion of C/EBPbeta gene resulted in greatly reducing hepatic lipogenic genes, acetyl CoA carboxylase, and fatty acid synthase and increasing the expression of beta-oxidation genes in the brown adipose tissue. CO(2) production was significantly higher in the C/EBPbeta(-/-) mice as was the level of uncoupling protein (UCP)-1 and UCP-3 in the muscle. In conclusion, the transcription factor C/EBPbeta is an important regulator in controlling lipid metabolism and in the development of diet-induced obesity.
Millward
Carrie A
CA
Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA.
Heaney
Jason D
JD
Sinasac
David S
DS
Chu
Eric C
EC
Bederman
Ilya R
IR
Gilge
Danielle A
DA
Previs
Stephen F
SF
Croniger
Colleen M
CM
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency* / Q000235:genetics*; D002245:Carbon Dioxide / Q000032:analysis; D017931:DNA Primers; D018752:Diet, Fat-Restricted; D004041:Dietary Fats; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000517:prevention & control*; D012016:Reference Values
D022782:CCAAT-Enhancer-Binding Protein-beta; D017931:DNA Primers; D004041:Dietary Fats; D002245:Carbon Dioxide