![conference banner](/images/conference-banner.jpeg)
Abstract
The liver plays a central role in the regulation of cholesterol homeostasis. Hepatic cholesterol content is maintained by a complex interplay between input and output pathways; alterations in the balance among these processes may lead to accumulation of excess cholesterol in body compartments with potentially deleterious consequences at the level of blood vessels (atherosclerosis) and biliary tract (gallstone disease). Molecular biology has brought new insights into this field. Nuclear receptors have been shown to play a key role in the “sensing” of intracellular cholesterol levels and in the triggering of metabolic responses via the sterol regulatory element binding protein (SREBP) cascade. A nuclear receptor for bile acids, farnesoid X receptor (FXR), has been identified and the molecular pathways underlying feedback inhibition of bile acid synthesis, the main mechanism of irreversible degradation of cholesterol, have been clarified. Such regulation involves a number of additional coactivators/corepressors of the transcription of the limiting enzyme of bile acid synthesis, cholesterol 7α-hydroxylase. Finally, the main transporters of biliary lipids (bile acids, phospholipids and cholesterol) have been described; most of them undergo transcriptional control by nuclear receptors, allowing regulation of biliary lipid efflux in conditions of different intracellular availability. Despite a body of evidence coming from experimental models the intimate mechanisms of regulation have not been clearly defined and direct evidence in humans is rather limited. This review will focus on the role of nuclear receptors in the regulation of hepatic cholesterol degradation and biliary lipid secretion, and on the theoretical applications from a pharmacotherapeutic perspective.
Keywords: Nuclear Receptors, Hepatic Cholesterol, Gallstone Disease, cholesterol homeostasis, metabolic responses, farnesoid X receptor (FXR), biliary lipid secretion, pharmacotherapeutic perspective
Current Medicinal Chemistry
Title: Nuclear Receptors as Potential Molecular Targets in Cholesterol Accumulation Conditions: Insights from Evidence on Hepatic Cholesterol Degradation and Gallstone Disease in Humans
Volume: 15 Issue: 22
Author(s): M. Bertolotti, C. Gabbi, C. Anzivino, L. Carulli, P. Loria and N. Carulli
Affiliation:
Keywords: Nuclear Receptors, Hepatic Cholesterol, Gallstone Disease, cholesterol homeostasis, metabolic responses, farnesoid X receptor (FXR), biliary lipid secretion, pharmacotherapeutic perspective
Abstract: The liver plays a central role in the regulation of cholesterol homeostasis. Hepatic cholesterol content is maintained by a complex interplay between input and output pathways; alterations in the balance among these processes may lead to accumulation of excess cholesterol in body compartments with potentially deleterious consequences at the level of blood vessels (atherosclerosis) and biliary tract (gallstone disease). Molecular biology has brought new insights into this field. Nuclear receptors have been shown to play a key role in the “sensing” of intracellular cholesterol levels and in the triggering of metabolic responses via the sterol regulatory element binding protein (SREBP) cascade. A nuclear receptor for bile acids, farnesoid X receptor (FXR), has been identified and the molecular pathways underlying feedback inhibition of bile acid synthesis, the main mechanism of irreversible degradation of cholesterol, have been clarified. Such regulation involves a number of additional coactivators/corepressors of the transcription of the limiting enzyme of bile acid synthesis, cholesterol 7α-hydroxylase. Finally, the main transporters of biliary lipids (bile acids, phospholipids and cholesterol) have been described; most of them undergo transcriptional control by nuclear receptors, allowing regulation of biliary lipid efflux in conditions of different intracellular availability. Despite a body of evidence coming from experimental models the intimate mechanisms of regulation have not been clearly defined and direct evidence in humans is rather limited. This review will focus on the role of nuclear receptors in the regulation of hepatic cholesterol degradation and biliary lipid secretion, and on the theoretical applications from a pharmacotherapeutic perspective.
Export Options
About this article
Cite this article as:
Bertolotti M., Gabbi C., Anzivino C., Carulli L., Loria P. and Carulli N., Nuclear Receptors as Potential Molecular Targets in Cholesterol Accumulation Conditions: Insights from Evidence on Hepatic Cholesterol Degradation and Gallstone Disease in Humans, Current Medicinal Chemistry 2008; 15 (22) . https://dx.doi.org/10.2174/092986708785747544
DOI https://dx.doi.org/10.2174/092986708785747544 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the Treatment of Chronic Inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Psoriasis and Atherosclerosis: Is There a Need For Novel Biomarkers Assessing Cardiovascular Risk?
Current Pharmaceutical Design Relationship Between Cigarette Smoking and Other Coronary Risk Factors in Atherosclerosis: Risk of Cardiovascular Disease and Preventive Measures
Current Pharmaceutical Design Platelet Resistance to the Anti-Aggregating Agents in the Insulin Resistant States
Current Diabetes Reviews Anti-Seizure Medications and Estradiol for Neuroprotection in Epilepsy: The 2013 Update
Recent Patents on CNS Drug Discovery (Discontinued) Drug Development of Small-Molecule Inhibitors of AD-Relevant Kinases as Novel Perspective Multitargeted Approach
Current Alzheimer Research Neuroprotective Actions of Flavones and Flavonols: Mechanisms and Relationship to Flavonoid Structural Features
Central Nervous System Agents in Medicinal Chemistry Neuroprotective Efficacy of the Peroxisome Proliferator-Activated Receptor-γ Ligand in Chronic Cerebral Hypoperfusion
Current Neurovascular Research Clinical Relevance of Apolipoprotein E Genotyping Based on a Family History of Alzheimer's Disease
Current Alzheimer Research A Dig Deep to Scout the Pharmacological and Clinical Facet of Garlic (<i>Allium sativum</i>)
Current Traditional Medicine The Role of Cannabinoids in Inflammatory Modulation of Allergic Respiratory Disorders, Inflammatory Pain and Ischemic Stroke
Current Drug Targets The Effect of Acupuncture on Enteral Nutrition and Gastrointestinal Dynamics in Patients Who Have Suffered a Severe Stroke
Current Neurovascular Research Mitochondrion-Specific Antioxidants as Drug Treatments for Alzheimer Disease
CNS & Neurological Disorders - Drug Targets The Na+/H+ Exchanger: A Target for Cardiac Therapeutic Intervention
Current Drug Targets - Cardiovascular & Hematological Disorders Editorial (Thematic Issue: Endocrine Disorders and Cognitive Function in the Elderly)
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Mediterranean Diet and Risk of Dementia
Current Alzheimer Research Immunomodulatory Effect of Phytoactive Compounds on Human Health: A Narrative Review Integrated with Bioinformatics Approach
Current Topics in Medicinal Chemistry Radiopharmaceutical: Revolutionary Agents for Diagnosis
Current Radiopharmaceuticals Neuroinflammatory Markers in Spontaneously Hypertensive Rat Brain: An Immunohistochemical Study
CNS & Neurological Disorders - Drug Targets Microglial dependent protective effects of neuroactive steroids
CNS & Neurological Disorders - Drug Targets Calcium Channel Blockers in Obesity-Related Hypertension
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)