Mice With a Deletion in the Gene for CCAAT/Enhancer-Binding Protein β Are Protected Against Diet-Induced Obesity

Abstract

The CCAAT/enhancer-binding protein ␤ (C/EBP␤) is required for adipocyte differentiation and maturation. We have studied the role of the transcription factor, C/EBP␤, in the development of diet-induced obesity. Mice with a deletion in the gene for C/EBP␤ (C/EBP␤ ؊/؊ ) and wild-type mice were fed a high-fat diet (60% fat) for 12 weeks. The C/EBP␤ ؊/؊ mice lost body fat, whereas the wild-type mice increased their total body fat on a high-fat diet. The C/EBP␤ ؊/؊ 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/EBP␤ gene resulted in greatly reducing hepatic lipogenic genes, acetyl CoA carboxylase, and fatty acid synthase and increasing the expression of ␤-oxidation genes in the brown adipose tissue. CO 2 production was significantly higher in the C/EBP␤ ؊/؊ mice as was the level of uncoupling protein (UCP)-1 and UCP-3 in the muscle. In conclusion, the transcription factor C/EBP␤ is an important regulator in controlling lipid metabolism and in the development of diet-induced obesity. Diabetes 56: 161-167, 2007

Postnatal Programming of Glucocorticoid Metabolism in Rats Modulates High-Fat Diet–Induced Regulation of Visceral Adipose Tissue Glucocorticoid Exposure and Sensitivity and Adiponectin and Proinflammatory Adipokines Gene Expression in Adulthood

“…Conversely, although both C/EBP␣ and -␤ are required for the basal transcriptional activity of 11␤-HSD-1 in 3T3-L1, a preadipocyte cell line, C/EBP␤ is strongly involved in forskolin-induced stimulation of 11␤-HSD-1 gene transcription (47). Interestingly, it has recently been demonstrated that mice with a deletion in the gene for C/EBP␤ are protected against diet-induced obesity (48).…”

CCAAT/enhancer binding protein β-deficiency enhances type 1 diabetic bone phenotype by increasing marrow adiposity and bone resorption

“…Although many studies have demonstrated the importance of C/EBP␤ for adipocyte phenotype in vitro (9,12,64,66) and in vivo (40,50,54), effects of C/EBP␤ on bone marrow adiposity have not been extensively examined. Our findings demonstrate no significant difference between marrow adipocyte numbers in wild-type and C/EBP␤ Ϫ/Ϫ mice (Fig.…”

“…Overexpression of C/EBP␤ alone induces adipocyte differentiation in NIH-3T3 fibroblasts, while LIP overexpression can prevent it (64,66). Total deficiency of C/EBP␤ protects mice from obesity and reduces body fat mass (40,50,54). Combined knockout of C/EBP␤ and C/EBP␦ leads to an even greater block to the adipocyte phenotype and adiposity (58).…”

CCAAT/enhancer binding protein α, β and δ gene variants: associations with obesity related phenotypes in the Leeds Family Study

“…[37][38][39][40][41][42][43] Furthermore, studies Genotype comparisons carried out using log-transformed data and adjusted for age and sex. Two SNPs from CEBPB were associated with WHR and leptin when considered separately, but only one was considered in multivariable analysis because of strong linkage dysequilibrium in mice deficient in C/EBPa or C/EBPβ demonstrate an essential role for C/EBPa in the development of white adipose tissue 35,44 and resistance to the development of obesity is associated with absence of C/EBPβ, 45,46 supporting a possible role for altered expression of C/EBPa and C/EBPβ in obesity.…”