Lise-Lotte Vedin

Karolinska Institutet | KI · Department of Laboratory Medicine

Liver X receptors (LXRs) are nuclear transcription factors important in the regulation of cholesterol transport, and glucose and fatty acid metabolism. The antiproliferative role of LXRs has been studied in a variety of malignancies and may represent a therapeutic opportunity in cancers lacking targeted therapies, such as triple-negative breast can...

The synchronization of circadian clock depends on a central pacemaker located in the suprachiasmatic nuclei. However, the potential feedback of peripheral signals on the central clock remains poorly characterized. To explore whether peripheral organ circadian clocks may affect the central pacemaker, we used a chimeric model in which mouse hepatocyt...

The circadian clock is an evolutionarily acquired gene network that synchronizes physiological processes to adapt homeostasis to the succession of day and night. While most mammalian cells have a circadian clock, their synchronization at the body-level depends on a central pacemaker located in the suprachiasmatic nuclei of the hypothalamus that int...

Background Sterol O-Acyltransferase 2 (Soat2) encodes acyl-Coenzyme A:cholesterol acyltransferase 2 (ACAT2), which synthesizes cholesteryl esters in hepatocytes and enterocytes fated either to storage or to secretion into nascent triglyceride-rich lipoproteins. Objectives We aimed to unravel the molecular mechanisms leading to reduced hepatic stea...

Background and aims: Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver-humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore the...

Supporting Information from Minniti et al., Insights From Liver-Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR-Agonist Pharmacodynamics in Humans, Hepatology (2019).

Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central ro...

Thyroid hormones have important effects on cellular development, growth, and metabolism and are necessary for the healthy function of almost all tissues. Hyperthyroid patients with excess thyroid hormone levels experience tachycardia, fatigue, muscle wasting, and osteoporosis. However, although high thyroid hormone levels have adverse effects, effo...

Aim: Animal models are commonly used to study human metabolic diseases despite major differences in hepatic lipid metabolism. Liver-humanized mouse is an improved model to study human lipoprotein metabolism, but details on donor specificity are still lacking. Thus, we aimed to further investigate lipoprotein metabolism in liver-humanized mouse and...

Hepatitis C Virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LD) for steatosis d...

Introduction: Liver X receptors (LXRs) are nuclear receptors with well-known functions in cholesterol transport, fatty acid and glucose metabolism, and modulation of immune responses. Natural and synthetic ligands have been identified and are under development for the treatment of metabolic and inflammatory conditions and diseases. There is mounti...

Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect early and is often resistant to standard chemotherapeutic options, contributing to extremely poor disease outcomes. Members of the nuclear receptor superfamily carry out essential biological functions such as hormone signaling and are successfully targeted in the treatment of endocrine-...

We examined the function of the oxysterol receptors (LXRs) in inflammatory bowel disease (IBD) through studying dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and by elucidating molecular mechanisms underlying their anti-inflammatory action. We observed that Lxr-deficient mice are more susceptib...

Unlabelled: Liver X receptor (LXR) activation stimulates triglyceride (TG) accumulation in the liver. Several lines of evidence indicate that estradiol-17β (E2) reduces TG levels in the liver; however, the molecular mechanism underlying the E2 effect remains unclear. Here, we show that administration of E2 attenuated sterol regulatory element-bind...

The oxysterol receptors LXRα and LXRβ are members of the nuclear receptor family and established transcriptional regulators of lipid metabolism with additional anti-inflammatory functions. Recent investigations have indicated an important role of LXRs in the control of proliferation. Here we further extend this knowledge to human colon cancer cells...

Liver X receptors (LXRs) are members of the nuclear receptor family of ligand-dependent transcription factors and have established functions as regulators of cholesterol, glucose, and fatty acid metabolism and inflammatory responses. Published reports of anti-proliferative effects of synthetic LXR ligands on breast, prostate, ovarian, lung, skin, a...

The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads. We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidog...

35 most upregulated genes in SF-1 RNAi-treated cells. (PDF)

50 first hits in DAVID functional annotation chart of siSF-1 microarray. (PDF)

35 most downregulated genes in SF-1 RNAi-treated cells. (PDF)

35 most downregugulated genes in SF-1 RNAi+cAMP-treated cells. (PDF)

35 most upregulated genes in cAMP-treated cells. (PDF)

35 most downregulated genes in cAMP-treated cells. (PDF)

35 most upregugulated genes inRNF31 RNAi+cAMP treated cells. (PDF)

35 most downregugulated genes inRNF31 RNAi+cAMP treated cells. (PDF)

35 most upregugulated genes in SF-1 RNAi+cAMP-treated cells. (PDF)

35 most upregulated genes in RNF31 RNAi-treated cells. (PDF)

35 most downregulated genes in RNF31 RNAi-treated cells. (PDF)

The oxysterol receptors [liver X receptors (LXRα and LXRβ)] regulate cholesterol and lipid biosynthesis and several studies link dysregulation of these metabolic pathways to aberrant cell growth. Here, we show that activation of LXR significantly reduced proliferation in several human breast cancer cells lines. LXR suppressed messenger RNA and/or p...