Nuclear receptors are regulatory proteins within the cell nucleus that can directly bind to a variety of hormones, metabolites and pharmaceuticals. Binding affects the activity of these proteins, causing them to switch genes on or off that in turn leads to increased or decreased production of the proteins that carry out diverse functions within the cell.
Numerous nuclear receptors are known as master regulators of lipid metabolism and homeostasis. Latest research indicates that these receptors also play important roles in the control of inflammation via mechanisms that remain to be clarified.
A team led by Professor Eckardt Treuter has now investigated the molecular mechanisms of how the nuclear lipid receptors LRH-1 and LXR inhibit inflammatory gene expression in liver during the so-called acute phase response. The study identified GPS2, a protein that directly interacts with receptors, as a central component of a sophisticated protein network – or ‘genomic positioning system’ – determining where and when these lipid receptors can function anti-inflammatory.
The identified pathway connects metabolism and inflammation and is therefore relevant for the understanding of metabolic diseases such as diabetes and atherosclerosis. The researchers suspect even broader roles of related pathways in different tissues linked to metabolic diseases and to cancers.
“We are now closer to understanding, at the molecular level, how dys-regulation of individual components of these pathways causes alterations in gene expression that contribute to the development of metabolic diseases linked to inflammation. This knowledge may open up novel pharmacological interventions. For example, drugs that stabilize receptor interactions with GPS2 could possibly trigger the anti-inflammatory pathway”, Eckardt Treuter says.
Publication: ‘GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXR in the hepatic acute phase response’, Nicolas Venteclef, Tomas Jakobsson, Anna Ehrlund, Anastasios Damdimopoulos, Laura Mikkonen, Ewa Ellis, Lisa-Mari Nilsson, Paolo Parini, Olli A. Jänne, Jan-Åke Gustafsson, Knut R. Steffensen & Eckardt Treuter, Genes & Development, online 16 February 2010.
For more information, please contact:
Professor Eckardt Treuter
Department of Biosciences and Nutrition
Tel. +46 (0)8-6089162 or +46 (0)70-7563805
E-mail: eckardt.treuter@ki.se
Press Officer Katarina Sternudd
Tel: +46 (0)8-524 838 95
E-mail: Katarina.sternudd@ki.se
Karolinska Institutet is one of the leading medical universities in Europe. Through research and education, Karolinska Institutet contributes to improving human health. Each year, the Nobel Assembly at Karolinska Institutet awards the Nobel Prize in Physiology or Medicine. For more information, visit ki.se.
28 February, 2023 - Karolinska Institutet
Following a successful pilot study, an online anonymous treatment program aimed at reducing child sexual abuse by providing treatment to individuals who exhibit sexual urges towards children is being launched across the EU. It is now available in Swedish, German, and Portuguese as well as in an updated English version. The treatment program, which has […]
29 April, 2021 - Karolinska Institutet
Researchers at Karolinska Institutet and the Public Health Agency of Sweden have studied newborn babies whose mothers tested positive for SARS-CoV-2 during pregnancy or childbirth. The results show that although babies born of test-positive mothers are more likely to be born early, extremely few were infected with COVID-19. The study, which is published in the […]
27 April, 2020 - Karolinska Institutet
Only about five per cent of the babies born to mothers with hepatitis C are themselves infected by the disease. A possible reason for this low figure is that the baby’s immune system has already destroyed the virus before birth. A new study from researchers at KI and published in the journal Gut reveals clear […]
7 April, 2020 - Karolinska Institutet
People with celiac disease have increased risk of dying prematurely, despite increased awareness of the disease in recent years and better access to gluten-free food. This is according to a new study from Karolinska Institutet in Sweden and Columbia University in the U.S. published in the prestigious journal JAMA. Celiac disease was linked to increased […]
Expertsvar, The Swedish Research Council, Hantverkargatan 11B, Stockholm SWEDENPhone +46(0)8 546 44 000
P.O. Box 1035, SE-101 38 Stockholm, expertsvar@vr.se
Information about cookies will open in a new window
