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

• Published in: Diabetes (New York, N.Y.) Vol. 56; no. 1; pp. 161 - 167
• Main Authors: MILLWARD, Carrie A, HEANEY, Jason D, SINASAC, David S, CHU, Eric C, BEDERMAN, Ilya R, GILGE, Danielle A, PREVIS, Stephen F, CRONIGER, Colleen M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2007
• Subjects: Animals; Base Sequence; Biological and medical sciences; Body Weight; Carbon Dioxide - analysis; CCAAT-Enhancer-Binding Protein-beta - deficiency; CCAAT-Enhancer-Binding Protein-beta - genetics; Diabetes; Diabetes mellitus; Diabetes research; Diabetes. Impaired glucose tolerance; Diet, Fat-Restricted; Dietary Fats; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene Deletion; Genetic aspects; Medical sciences; Metabolic diseases; Mice; Mice, Knockout; Obesity; Obesity - genetics; Obesity - prevention & control; Reference Values; Endocrinopathy; Obesity; Diabetes mellitus; Rodentia; Nutrition disorder; Feeding; Binding protein; Vertebrata; Mammalia; Gene; Diet; Mouse; Animal; Deletion; Nutritional status
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db06-0310

Mice With a Deletion in the Gene for CCAAT/Enhancer-Binding Protein β Are Protected Against Diet-Induced Obesity Carrie A. Millward 1 , Jason D. Heaney 2 , David S. Sinasac 2 , Eric C. Chu 1 , Ilya R. Bederman 1 , Danielle A. Gilge 1 , Stephen F. Previs 1 and Colleen M. Croniger 1 1 Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 2 Department of Genetics, Case Western Reserve University, Cleveland, Ohio Address correspondence and reprint requests to Colleen M. Croniger, Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106. E-mail: cmc6{at}case.edu Abstract The CCAAT/enhancer-binding protein β (C/EBPβ) is required for adipocyte differentiation and maturation. We have studied the role of the transcription factor, C/EBPβ, in the development of diet-induced obesity. Mice with a deletion in the gene for C/EBPβ (C/EBPβ −/− ) and wild-type mice were fed a high-fat diet (60% fat) for 12 weeks. The C/EBPβ −/− mice lost body fat, whereas the wild-type mice increased their total body fat on a high-fat diet. The C/EBPβ −/− 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/EBPβ gene resulted in greatly reducing hepatic lipogenic genes, acetyl CoA carboxylase, and fatty acid synthase and increasing the expression of β-oxidation genes in the brown adipose tissue. CO 2 production was significantly higher in the C/EBPβ −/− mice as was the level of uncoupling protein (UCP)-1 and UCP-3 in the muscle. In conclusion, the transcription factor C/EBPβ is an important regulator in controlling lipid metabolism and in the development of diet-induced obesity. ACC, acetyl CoA carboxylase AOX, acyl-CoA oxidase BAT, brown adipose tissue C/EBPβ, CCAAT/enhancer-binding protein β CPT, carnitine palmitoyltransferase CRE, cAMP responsive element–binding protein regulatory region FAS, fatty acid synthase FFA, free fatty acid HMG, hydroxymethylglutaryl LCAD, long acyl-CoA dehydrogenase PPARγ, peroxisome proliferator–activated receptor γ SCD-1, sterol CoA desaturase-1 SREBP-1, sterol regulatory element–binding protein-1 UCP, uncoupling protein Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted September 18, 2006. Received March 7, 2006. DIABETES