Abstract
Obesity and type 2 diabetes have reached epidemic proportions worldwide. These metabolic disorders, particularly obesity, are characterised by increased basal sympathetic nervous system (SNS) activity but an impaired sympathetic response to certain stimuli, such as insulin. Although targeting the SNS may seem an attractive avenue for the pharmacological prevention and treatment of obesity and related metabolic disorders, it remains unknown whether changes in SNS tone are primary and contribute to the development of these metabolic conditions or whether they develop secondary to the obese state. This question can be answered by the study of insulinresistant individuals prior to the development of obesity and type 2 diabetes. Using this model, it has been shown that early insulin resistance is associated with increased SNS activity in genetically-predisposed humans. It has been suggested that in insulin-resistant states, hyperinsulinaemia is the initiating factor that increases sympathetic neural activity. Over time, adrenoreceptor down-regulation and/or reduced sensitivity are likely to develop, resulting in reduced sympathetic responsiveness. In the postprandial state, this will lead to impaired diet-induced thermogenesis and post-prandial fat oxidation, promoting the accumulation of body fat. More recent evidence demonstrates that stress-induced SNS overactivity up-regulates Neuropeptide Y, an orexigenic hormone, and its Y2 receptor, in visceral adipose tissue, the fat depot most strongly linked to insulin resistance and type 2 diabetes. There is evidence that SNS overactivity specifically contributes to the development of abdominal obesity via this pathway, which could represent a novel target for the prevention and treatment of abdominal obesity and related metabolic consequences.
Keywords: Autonomic nervous system, sympathetic nervous system, insulin resistance, overweight, obesity, neuropeptide Y, Y2 receptor
Current Pharmaceutical Design
Title: Role of the Autonomic Nervous System and Neuropeptides in the Development of Obesity in Humans: Targets for Therapy?
Volume: 14 Issue: 18
Author(s): Jerry R. Greenfield and Lesley V. Campbell
Affiliation:
Keywords: Autonomic nervous system, sympathetic nervous system, insulin resistance, overweight, obesity, neuropeptide Y, Y2 receptor
Abstract: Obesity and type 2 diabetes have reached epidemic proportions worldwide. These metabolic disorders, particularly obesity, are characterised by increased basal sympathetic nervous system (SNS) activity but an impaired sympathetic response to certain stimuli, such as insulin. Although targeting the SNS may seem an attractive avenue for the pharmacological prevention and treatment of obesity and related metabolic disorders, it remains unknown whether changes in SNS tone are primary and contribute to the development of these metabolic conditions or whether they develop secondary to the obese state. This question can be answered by the study of insulinresistant individuals prior to the development of obesity and type 2 diabetes. Using this model, it has been shown that early insulin resistance is associated with increased SNS activity in genetically-predisposed humans. It has been suggested that in insulin-resistant states, hyperinsulinaemia is the initiating factor that increases sympathetic neural activity. Over time, adrenoreceptor down-regulation and/or reduced sensitivity are likely to develop, resulting in reduced sympathetic responsiveness. In the postprandial state, this will lead to impaired diet-induced thermogenesis and post-prandial fat oxidation, promoting the accumulation of body fat. More recent evidence demonstrates that stress-induced SNS overactivity up-regulates Neuropeptide Y, an orexigenic hormone, and its Y2 receptor, in visceral adipose tissue, the fat depot most strongly linked to insulin resistance and type 2 diabetes. There is evidence that SNS overactivity specifically contributes to the development of abdominal obesity via this pathway, which could represent a novel target for the prevention and treatment of abdominal obesity and related metabolic consequences.
Export Options
About this article
Cite this article as:
Greenfield R. Jerry and Campbell V. Lesley, Role of the Autonomic Nervous System and Neuropeptides in the Development of Obesity in Humans: Targets for Therapy?, Current Pharmaceutical Design 2008; 14 (18) . https://dx.doi.org/10.2174/138161208784746716
DOI https://dx.doi.org/10.2174/138161208784746716 |
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
-
High Throughput Mutation Screening by Automated Capillary Electrophoresis
Combinatorial Chemistry & High Throughput Screening Hypoxia as an Initiator of Neuroinflammation: Microglial Connections
Current Neuropharmacology Implication of Gut Microbiota in Human Health
CNS & Neurological Disorders - Drug Targets The Effect of Licorice Drink on the Systemic Exposure of Verapamil in Rabbits
Drug Metabolism Letters Recombinant Human Insulin-Like Growth Factor-1: A New Cardiovascular Disease Treatment Option?
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial (Thematic Issue: Health Impact and Management of a Disrupted Circadian Rhythm and Sleep in Critical Illnesses)
Current Pharmaceutical Design Seeking Novel Targets for Improving In Vivo Macrophage-Specific Reverse Cholesterol Transport: Translating Basic Science into New Therapies for the Prevention and Treatment of Atherosclerosis
Current Vascular Pharmacology The Progress Towards the Development of DHQO Derivatives and Related Analogues with Inotropic Effects
Mini-Reviews in Medicinal Chemistry Fc-independent Phagocytosis: Implications for IVIG and other Therapies in Immune-mediated Thrombocytopenia
Cardiovascular & Hematological Disorders-Drug Targets Using Properties of Tumor Microenvironments for Controlling Local, On-Demand Delivery from Biopolymer-Based Nanocarriers
Current Pharmaceutical Design Electronic Noses in Medical Diagnostics
Current Medicinal Chemistry Electrophysiologic Considerations After Sudden Cardiac Arrest
Current Cardiology Reviews Effect of Dietary Education on Cardiovascular Risk Factors in Rheumatoid Arthritis Patients
Current Rheumatology Reviews Renal Phosphate Handling in Antiretroviral-naive HIV-Infected Patients
Infectious Disorders - Drug Targets Refined Purification of Large Amounts of Rat cvHsp/HspB7 and Partial Biological Characterization In Vitro
Protein & Peptide Letters Lentiviral Vectors: A Versatile Tool to Fight Cancer
Current Molecular Medicine Solution NMR Study of the Transmembrane Domain of Single-Span Membrane Proteins: Opportunities and Strategies
Current Protein & Peptide Science Hypertension in Obstructive Sleep Apnoea
Vascular Disease Prevention (Discontinued) Inflammation-Mediating Proteases: Structure, Function in (Patho) Physiology and Inhibition
Protein & Peptide Letters Synthesis and Cytotoxic Activity of 4-Aryl-4H-chromeno[4,3-d] [1,2,3] selenadiazoles
Letters in Drug Design & Discovery