Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Bart Staels, University of Lille
- Second opponent: Senior Lecturer Eili Tranheim Kase, University of Oslo
- Third member and chair of the evaluation committee: Professor Bente E. Halvorsen, University of Oslo
Chair of the Defence
Associate Professor Ragnhild Eskeland, University of Oslo
Principal Supervisor
Associate Professor Thomas Sæther, University of Oslo
Summary
Humans have limited capacity to store energy as carbohydrates, thus excess energy is converted to fat by de novo lipogenesis. Ectopic fat storage in adipose and liver is driving development of diabetes and cardiovascular disease. The cholesterol-activated nuclear receptor LXR makes up a transcriptional network in liver together with SREBP-1c and the glucose-sensing transcription factor ChREBP that regulates lipogenic and glycolytic genes. The aim of this thesis was to investigate the role of LXRs and the posttranslational modification O-GlcNAc in hepatic lipogenesis in response to high carbohydrate conditions. The presented data show that LXRs regulate hepatic lipogenic gene expression, independent of insulin signaling. This is propagated through increased nuclear O-GlcNAc signaling and ChREBPα activity. Furthermore, LXRα regulates ChREBPα activity and lipogenesis in glucose-fed, but not fructose-fed mice liver. Finally, LXRα directly regulates ChREBPα target genes. This is enforced by a physical interaction between LXRα and ChREBPα. Together these studies contributes to a deeper understanding of the intricate fine-tuning of glucose and lipid metabolism in the liver.
Additional information
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