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.
Författare
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.
Avdelning/ar
Publiceringsår
2008
Språk
Engelska
Sidor
4880-4886
Publikation/Tidskrift/Serie
Journal of Clinical Endocrinology and Metabolism
Volym
93
Issue
12
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Endocrinology and Diabetes
Status
Published
Forskningsgrupp
- Genomics, Diabetes and Endocrinology
ISBN/ISSN/Övrigt
- ISSN: 1945-7197