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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.

Olofsson, Louise E; Orho-Melander, Marju LU ; William-Olsson, Lena; Sjöholm, Kajsa; Sjöström, Lars; Groop, Leif LU ; Carlsson, Björn; Carlsson, Lena M S and Olsson, Bob (2008) In Journal of Clinical Endocrinology and Metabolism 93(12). p.4880-4886
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
93
issue
12
pages
4880 - 4886
publisher
The Endocrine Society
external identifiers
  • wos:000261396900043
  • pmid:18765514
  • scopus:57349119903
ISSN
1945-7197
DOI
10.1210/jc.2008-0574
language
English
LU publication?
yes
id
9753b8d2-5229-4f79-afc6-8a13eedb861d (old id 1243473)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18765514?dopt=Abstract
date added to LUP
2008-10-03 15:17:02
date last changed
2017-08-20 03:59:19
@article{9753b8d2-5229-4f79-afc6-8a13eedb861d,
  abstract     = {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.},
  author       = {Olofsson, Louise E and Orho-Melander, Marju and William-Olsson, Lena and Sjöholm, Kajsa and Sjöström, Lars and Groop, Leif and Carlsson, Björn and Carlsson, Lena M S and Olsson, Bob},
  issn         = {1945-7197},
  language     = {eng},
  number       = {12},
  pages        = {4880--4886},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {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.},
  url          = {http://dx.doi.org/10.1210/jc.2008-0574},
  volume       = {93},
  year         = {2008},
}