This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Olofsson, L. E. Articles by Olsson, B. Search for Related Content PubMed PubMed Citation Articles by Olofsson, L. E. Articles by Olsson, B. Related Collections Lipid Diabetes and Insulin Metabolism

CCAAT/Enhancer Binding Protein (C/EBP) in Adipose Tissue Regulates Genes in Lipid and Glucose Metabolism and a Genetic Variation in C/EBP Is Associated with Serum Levels of Triglycerides

Department of Molecular and Clinical Medicine (L.E.O., K.S., L.S., B.C., L.M.S.C., B.O.), The Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden; Department of Clinical Sciences (M.O.-M., L.G.), Diabetes and Endocrinology Research Unit and Lund University Diabetes Center, Clinical Research Center, University Hospital Malmö, Lund University, 205 02 Malmö, Sweden; and AstraZeneca Research and Development (L.W.-O., B.C.), 431 83 Mölndal, Sweden

Address all correspondence and requests for reprints to: Bob Olsson, Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Vita stråket 15, 413 45 Gothenburg, Sweden. E-mail: bob.olsson{at}medic.gu.se.

Context: CCAAT/enhancer binding protein (C/EBP) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism.

Objective: The aim of the study was to test the hypothesis that adipose tissue C/EBP regulates genes in lipid and glucose metabolism and to test for an association between a polymorphism in C/EBP and metabolic parameters.

Design and Methods: Adipose tissue C/EBP mRNA expression was analyzed at four time points in obese subjects with (n = 12) and without (n = 12) the metabolic syndrome during caloric restriction (450 kcal/d for 16 wk) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBP was used to identify genes regulated by C/EBP in 3T3-L1 cells. Association between a genetic variation in C/EBP (rs12691) and metabolic parameters was tested in the Swedish Obese Subjects (SOS) study (n = 528) and replicated in Finnish individuals from the Botnia type 2 diabetes study (n = 4866).

Results: During caloric restriction, adipose tissue C/EBP mRNA levels were reduced in subjects with the metabolic syndrome (P = 0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBP regulated the expression of adiponectin; hexokinase 2; lipoprotein lipase; diacylglycerol O-acyltransferase 1 and 2; ATP-binding cassette, sub-family D, member 2; acyl-coenzyme A synthetase long-chain family member 1; CD36; and hydroxysteroid 11-β dehydrogenase 1. Furthermore, the expression of the human homologs, except adiponectin, correlated to C/EBP mRNA levels in human adipose tissue. The AA genotype of rs12691 was associated with higher serum triglyceride levels in the SOS study (P = 0.022), and this association was replicated in the Botnia study (P = 0.041).

Conclusions: Adipose tissue C/EBP regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBP is associated with triglycerides in two independent populations.

This article has been cited by other articles:

				Y.-S. Tsai, P.-J. Tsai, M.-J. Jiang, T.-Y. Chou, A. Pendse, H.-S. Kim, and N. Maeda Decreased PPAR{gamma} Expression Compromises Perigonadal-Specific Fat Deposition and Insulin Sensitivity Mol. Endocrinol., November 1, 2009; 23(11): 1787 - 1798. [Abstract] [Full Text] [PDF]

				S. Katari, N. Turan, M. Bibikova, O. Erinle, R. Chalian, M. Foster, J. P. Gaughan, C. Coutifaris, and C. Sapienza DNA methylation and gene expression differences in children conceived in vitro or in vivo Hum. Mol. Genet., October 15, 2009; 18(20): 3769 - 3778. [Abstract] [Full Text] [PDF]

				T. Juan, M. M. Veniant, J. Helmering, P. Babij, D. M. Baker, M. A. Damore, M. B. Bass, T. Gyuris, M. Chhoa, C.-M. Li, et al. Identification of three loci affecting HDL-cholesterol levels in a screen for chemically induced recessive mutations in mice J. Lipid Res., March 1, 2009; 50(3): 534 - 545. [Abstract] [Full Text] [PDF]