Abstract
The development of efficacious antiretroviral drugs that minimize adverse effects is a current challenge in HIV-1 therapy. Metabolic alterations reminiscent of the metabolic syndrome and overt lipodystrophy appear often in HIV-1-infected patients undergoing antiretroviral treatment. The etiopathogenesis of these alterations is complex, but lipotoxicity has recently emerged as a key concept for explaining the metabolic syndrome in HIV-1-infected patients, similarly to what has been observed in diseases such as obesity and genetic lipodystrophies. Antiretroviral drugs from distinct drug families may directly elicit such lipotoxic phenomena, via increased lipolysis, enhanced adipocyte apoptosis and impaired adipogenesis, which collectively lead to a reduced capacity of subcutaneous adipose tissue to enlarge to meet fat storage requirements. Thus, fatty acids that cannot be properly stored as triglycerides in subcutaneous adipose tissue are expected to accumulate in visceral fat as well as in organs and tissues, such as the pancreas, muscle and liver, leading to the pattern of metabolic alterations associated with abnormal ectopic fat accumulation, mainly insulin resistance. Inflammatory responses, evoked by the combined effects of antiretroviral drugs and the underlying HIV-1 infection, also contribute to lipotoxicity, reflecting the action of pro-inflammatory cytokines that enhance lipolytic activity in adipose tissue and impair adipogenesis. Minimizing the lipotoxic action of antiretroviral drugs is ultimately essential in reducing metabolic alterations in treated patients. Moreover, pharmacological strategies that reduce lipotoxicity and promote adipose tissue expandability can be expected to ameliorate the overall metabolic abnormalities in HIV-1-infected, antiretroviral-treated patients.
Keywords: Lipotoxicity, lipodystrophy, HIV, fatty acids, adipose tissue
Current Pharmaceutical Design
Title: Lipotoxicity on the Basis of Metabolic Syndrome and Lipodystrophy in HIV-1-Infected Patients Under Antiretroviral Treatment
Volume: 16 Issue: 30
Author(s): Marta Giralt, Julieta Diaz-Delfin, Jose M. Gallego-Escuredo, Joan Villarroya, Pere Domingo and Francesc Villarroya
Affiliation:
Keywords: Lipotoxicity, lipodystrophy, HIV, fatty acids, adipose tissue
Abstract: The development of efficacious antiretroviral drugs that minimize adverse effects is a current challenge in HIV-1 therapy. Metabolic alterations reminiscent of the metabolic syndrome and overt lipodystrophy appear often in HIV-1-infected patients undergoing antiretroviral treatment. The etiopathogenesis of these alterations is complex, but lipotoxicity has recently emerged as a key concept for explaining the metabolic syndrome in HIV-1-infected patients, similarly to what has been observed in diseases such as obesity and genetic lipodystrophies. Antiretroviral drugs from distinct drug families may directly elicit such lipotoxic phenomena, via increased lipolysis, enhanced adipocyte apoptosis and impaired adipogenesis, which collectively lead to a reduced capacity of subcutaneous adipose tissue to enlarge to meet fat storage requirements. Thus, fatty acids that cannot be properly stored as triglycerides in subcutaneous adipose tissue are expected to accumulate in visceral fat as well as in organs and tissues, such as the pancreas, muscle and liver, leading to the pattern of metabolic alterations associated with abnormal ectopic fat accumulation, mainly insulin resistance. Inflammatory responses, evoked by the combined effects of antiretroviral drugs and the underlying HIV-1 infection, also contribute to lipotoxicity, reflecting the action of pro-inflammatory cytokines that enhance lipolytic activity in adipose tissue and impair adipogenesis. Minimizing the lipotoxic action of antiretroviral drugs is ultimately essential in reducing metabolic alterations in treated patients. Moreover, pharmacological strategies that reduce lipotoxicity and promote adipose tissue expandability can be expected to ameliorate the overall metabolic abnormalities in HIV-1-infected, antiretroviral-treated patients.
Export Options
About this article
Cite this article as:
Giralt Marta, Diaz-Delfin Julieta, M. Gallego-Escuredo Jose, Villarroya Joan, Domingo Pere and Villarroya Francesc, Lipotoxicity on the Basis of Metabolic Syndrome and Lipodystrophy in HIV-1-Infected Patients Under Antiretroviral Treatment, Current Pharmaceutical Design 2010; 16 (30) . https://dx.doi.org/10.2174/138161210793563527
DOI https://dx.doi.org/10.2174/138161210793563527 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Snake Venom Prothrombin Activators Similar to Blood Coagulation Factor Xa
Current Drug Targets - Cardiovascular & Hematological Disorders Schizophrenia: A Systematic Review of the Disease State, Current Therapeutics and their Molecular Mechanisms of Action
Current Medicinal Chemistry Erectile Dysfunction as a Cardiovascular Risk Factor: Time to Step Up?
Current Vascular Pharmacology Cardio-Vascular Risks Associated with Clozapine Treatment
Current Psychiatry Reviews Cabazitaxel: A Novel Drug for Hormone-Refractory Prostate Cancer
Mini-Reviews in Medicinal Chemistry Moderate Hypothermia in the Management of Severe Traumatic Brain Injury: A Good Idea Proved Ineffective?
Current Pharmaceutical Design Model Systems for Pulmonary Infectious Diseases: Paradigms of Anthrax and Tuberculosis
Current Topics in Medicinal Chemistry Antiarrhythmic Therapy on Prevention of Postoperative Atrial Fibrillation in Patients After Heart Surgery
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Novel Atypical Antipsychotics: Metabolism and Therapeutic Drug Monitoring (TDM)
Current Drug Metabolism Antioxidant, Antimicrobial Activity and Medicinal Properties of Grewia asiatica L.
Medicinal Chemistry New Antipsychotics and Schizophrenia: A Review on Efficacy and Side Effects
Current Medicinal Chemistry Importance of Snake Venom Metalloproteinases in Cell Biology: Effects on Platelets,Inflammatory and Endothelial Cells
Current Pharmaceutical Design Natural Compounds A Weapon to Ameliorate Breast Cancer Cells: A Review
Anti-Cancer Agents in Medicinal Chemistry Gender Differences in Autonomic Control of the Cardiovascular System
Current Pharmaceutical Design N-Acetylcysteine for the Treatment of Obsessive-Compulsive Disorder
Current Psychiatry Reviews Giardiasis: Recent Progress in Chemotherapy and Drug Development (Hot Topic: Anti-Infective Agents Executive Editors: Mitchell A. Avery / Vassil St.) Georgiev
Current Pharmaceutical Design Targeting Soluble Epoxide Hydrolase for Inflammation and Pain - An Overview of Pharmacology and the Inhibitors
Inflammation & Allergy - Drug Targets (Discontinued) Microbial Polysaccharides and their Derivatives as Current and Prospective Pharmaceuticals
Current Pharmaceutical Design Synthesis, Characterization and Physico-chemical Properties of New 2-(4- Arylpiperazine-1-yl)-1-(3-methylbenzofuran-2-yl)ethanoles as Potential Antihypertensive Agents
Current Organic Chemistry Drug Therapy of Neuropathic Pain: Current Developments and Future Perspectives
Current Drug Targets