title: CCAAT/enhancer binding protein alpha (C/EBPalpha) in adipose tissue regulates genes in lipid and glucose metabolism and a genetic variation in C/EBPalpha is associated with serum levels of triglycerides.
abstract: BACKGROUND
  CCAAT/enhancer binding protein alpha (C/EBPalpha) 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/EBPalpha regulates genes in lipid and glucose metabolism and to test for an association between a polymorphism in C/EBPalpha and metabolic parameters.
  
  
  METHODS
  Adipose tissue C/EBPalpha 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/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a genetic variation in C/EBPalpha (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 = 4,866).
  
  
  RESULTS
  During caloric restriction, adipose tissue C/EBPalpha mRNA levels were reduced in subjects with the metabolic syndrome (P = 0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBPalpha 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-beta dehydrogenase 1. Furthermore, the expression of the human homologs, except adiponectin, correlated to C/EBPalpha 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/EBPalpha regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Vita stråket 15, 413 45 Gothenburg, Sweden.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Olofsson
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Lena
authors.initials: L
authors.lastname: William-Olsson
authors.forename: Kajsa
authors.initials: K
authors.lastname: Sjöholm
authors.forename: Lars
authors.initials: L
authors.lastname: Sjöström
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Björn
authors.initials: B
authors.lastname: Carlsson
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson