Abstract
A minute-to-minute crosstalk between the hypothalamic neuropeptide Y (NPY) network and the hormone leptin is essential for energy homeostasis. Leptin insufficiency i.e. lack of leptin restraint due to genetic and environmental factors on the hypothalamic NPY system confers obesity, a cluster of metabolic afflictions and shorter lifespan. A state-of-the-art gene transfer technology using recombinant adeno-associated viral vector to overcome hypothalamic leptin insufficiency was employed in rodent models of obesity, metabolic syndrome and shorter lifespan. Our findings show that life-long tonic repression of NPY system with a stable increase in leptin availability in the hypothalamus prevented the age-related and high fat-diet-induced obesity, hyperinsulinemia and diabetes and extended lifespan. Additional health benefits include increased energy expenditure and normalization of neuroendocrine control on reproduction, and promotion of brain and bone growth. We propose that central leptin gene therapy or novel long-acting leptin mimetics should be tested clinically to decelerate the worldwide epidemic of obesity, diabetes and shortened lifespan.
Keywords: Hypothalamic NPY, leptin gene therapy, obesity, diabetes, metabolic syndrome, bone growth
Current Topics in Medicinal Chemistry
Title: Global Life-Long Health Benefits of Repression of Hypothalamic NPY System by Central Leptin Gene Therapy
Volume: 7 Issue: 17
Author(s): Satya P. Kalra
Affiliation:
Keywords: Hypothalamic NPY, leptin gene therapy, obesity, diabetes, metabolic syndrome, bone growth
Abstract: A minute-to-minute crosstalk between the hypothalamic neuropeptide Y (NPY) network and the hormone leptin is essential for energy homeostasis. Leptin insufficiency i.e. lack of leptin restraint due to genetic and environmental factors on the hypothalamic NPY system confers obesity, a cluster of metabolic afflictions and shorter lifespan. A state-of-the-art gene transfer technology using recombinant adeno-associated viral vector to overcome hypothalamic leptin insufficiency was employed in rodent models of obesity, metabolic syndrome and shorter lifespan. Our findings show that life-long tonic repression of NPY system with a stable increase in leptin availability in the hypothalamus prevented the age-related and high fat-diet-induced obesity, hyperinsulinemia and diabetes and extended lifespan. Additional health benefits include increased energy expenditure and normalization of neuroendocrine control on reproduction, and promotion of brain and bone growth. We propose that central leptin gene therapy or novel long-acting leptin mimetics should be tested clinically to decelerate the worldwide epidemic of obesity, diabetes and shortened lifespan.
Export Options
About this article
Cite this article as:
Kalra P. Satya, Global Life-Long Health Benefits of Repression of Hypothalamic NPY System by Central Leptin Gene Therapy, Current Topics in Medicinal Chemistry 2007; 7 (17) . https://dx.doi.org/10.2174/156802607782340993
DOI https://dx.doi.org/10.2174/156802607782340993 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Metabolism and Pharmacological Mechanisms of Active Ingredients in <i>Erigeron breviscapus</i>
Current Drug Metabolism Transplacental Transfer of Antiretroviral Drugs and Newborn Birth Weight in HIV-Infected Pregnant Women
Current HIV Research Vascular Risk Factors and Lesions of Vascular Nature in Magnetic Resonance as Predictors of Progression to Dementia in Patients with Mild Cognitive Impairment
Current Alzheimer Research Functional Profiles of Human Umbilical Cord-Derived Adult Mesenchymal Stem Cells in Obese/Diabetic Versus Healthy Women
Current Diabetes Reviews Coronary Risk Factors in the Elderly: Their Interactions and Treatment
Current Pharmaceutical Design Recent Developments in the Search for Biomarkers for the Diagnosis and Monitoring of Diabetes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Inflammation and Mood Disorders: Proinflammatory Cytokines and the Pathogenesis of Depression
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Identification of a RhoA- and SRF-Dependent Mechanism of Androgen Action that is Associated with Prostate Cancer Progression
Current Drug Targets Mastering the Treatment of Diabetes Mellitus Type 1 in Childhood and Adolescence
Current Pediatric Reviews Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for New Anti-Diabetic Agent
Current Topics in Medicinal Chemistry Modulation of Platelet Function and Signaling by Flavonoids
Mini-Reviews in Medicinal Chemistry Patent Selections
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease
Current Pharmaceutical Design Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis
Current Alzheimer Research A Primary Reduced TCA Flux Governs Substrate Oxidation in T2D Skeletal Muscle
Current Diabetes Reviews Metformin for Prevention and Treatment of Colon Cancer: A Reappraisal of Experimental and Clinical Data
Current Drug Targets Long-term Exposure to Cadmium in Food and Cigarette Smoke, Liver Effects and Hepatocellular Carcinoma
Current Drug Metabolism Atenolol: Differences in Mode of Action Compared with other Antihypertensives.An Opportunity to Identify Features that Influence Outcome?
Current Pharmaceutical Design Genetics of Gestational Diabetes Mellitus
Current Medicinal Chemistry Should the Incorporation of Structural Alerts be Restricted in Drug Design? An Analysis of Structure-Toxicity Trends with Aniline-Based Drugs
Current Medicinal Chemistry