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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

C/EBP{alpha} in adipose tissue regulates genes in lipid and glucose metabolism and a genetic variation in C/EBP{alpha} is associated with serum levels of triglycerides.

Author

  • Louise E Olofsson
  • Marju Orho-Melander
  • Lena William-Olsson
  • Kajsa Sjöholm
  • Lars Sjöström
  • Leif Groop
  • Björn Carlsson
  • Lena M S Carlsson
  • Bob Olsson

Summary, in English

Context: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. Objective: To test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for association between a polymorphism in C/EBPalpha and metabolic parameters. Design and 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/day for 16 weeks) 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=4866). 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 ADIPOQ, HK2, LPL, DGAT 1 and 2, ABCD2, SLC27A2, CD36 and HSD11B1. Furthermore, the expression of the human homologues, except ADIPOQ, 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.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

2008

Language

English

Pages

4880-4886

Publication/Series

Journal of Clinical Endocrinology and Metabolism

Volume

93

Issue

12

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1945-7197