Abstract
Obesity is strongly associated with type 2 diabetes, hypertension, and hyperlipidemia, which is one of the leading causes of mortality and morbidity worldwide. It is now clear that gut hormones play a role in the regulation of body weight and represent therapeutic targets for the future treatment of obesity. Recent evidence demonstrated that dysregulation of adipocytokine functions seen in abdominal obesity may be involved in the pathogenesis of the metabolic syndrome. Angiotensinogen, the precursor of angiotensin (Ang) II, is produced primarily in the liver, but also in adipose tissue, where it is up-regulated during the development of obesity and involved in blood pressure regulation and adipose tissue growth. Importantly, blockade of the RAS attenuates weight gain and adiposity by enhanced energy expenditure. The favorable metabolic effects of telmisartan have been related to its Ang II receptor blockade and action as a partial agonist of peroxisome proliferators activated receptor (PPAR)-γ. PPARγ plays an important role in regulating carbohydrate and lipid metabolism, and ligands for PPARγ can improve insulin sensitivity and reduce triglyceride levels. We designed a comparative study of telmisartan and losartan in ApoE-deficient mice. Treatment with telmisartan or losartan significantly reduced the development of lipid-rich plaque. However, treatment with telmisartan significantly improved endothelial dysfunction and inhibited lipid accumulation in the liver. These favorable characteristics of telmisartan might be due to its action as a partial agonist of PPAR-γ, beyond its blood pressure-lowering effect, through Ang II blockade, which may be called “metabosartan”.
Keywords: Gut hormones, telmisartan, PPAR-γ, fatty liver
Current Vascular Pharmacology
Title: Obesity and Gastrointestinal Hormones-Dual Effect of Angiotensin II Receptor Blockade and a Partial Agonist of PPAR-γ
Volume: 9 Issue: 2
Author(s): Hironori Nakagami and Ryuichi Morishita
Affiliation:
Keywords: Gut hormones, telmisartan, PPAR-γ, fatty liver
Abstract: Obesity is strongly associated with type 2 diabetes, hypertension, and hyperlipidemia, which is one of the leading causes of mortality and morbidity worldwide. It is now clear that gut hormones play a role in the regulation of body weight and represent therapeutic targets for the future treatment of obesity. Recent evidence demonstrated that dysregulation of adipocytokine functions seen in abdominal obesity may be involved in the pathogenesis of the metabolic syndrome. Angiotensinogen, the precursor of angiotensin (Ang) II, is produced primarily in the liver, but also in adipose tissue, where it is up-regulated during the development of obesity and involved in blood pressure regulation and adipose tissue growth. Importantly, blockade of the RAS attenuates weight gain and adiposity by enhanced energy expenditure. The favorable metabolic effects of telmisartan have been related to its Ang II receptor blockade and action as a partial agonist of peroxisome proliferators activated receptor (PPAR)-γ. PPARγ plays an important role in regulating carbohydrate and lipid metabolism, and ligands for PPARγ can improve insulin sensitivity and reduce triglyceride levels. We designed a comparative study of telmisartan and losartan in ApoE-deficient mice. Treatment with telmisartan or losartan significantly reduced the development of lipid-rich plaque. However, treatment with telmisartan significantly improved endothelial dysfunction and inhibited lipid accumulation in the liver. These favorable characteristics of telmisartan might be due to its action as a partial agonist of PPAR-γ, beyond its blood pressure-lowering effect, through Ang II blockade, which may be called “metabosartan”.
Export Options
About this article
Cite this article as:
Nakagami Hironori and Morishita Ryuichi, Obesity and Gastrointestinal Hormones-Dual Effect of Angiotensin II Receptor Blockade and a Partial Agonist of PPAR-γ, Current Vascular Pharmacology 2011; 9 (2) . https://dx.doi.org/10.2174/157016111794519291
DOI https://dx.doi.org/10.2174/157016111794519291 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...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
-
TH2 Cytokines and Associated Transcription Factors as Therapeutic Targets in Asthma
Current Drug Targets - Inflammation & Allergy Diltiazem Analogues: The Last Ten Years on Structure Activity Relationships
Current Medicinal Chemistry A Neurotrophic Rationale for the Therapy of Neurodegenerative Disorders
Current Alzheimer Research Circulating Aminopeptidase Activities in Men and Women with Essential Hypertension
Current Medicinal Chemistry Editorial (Alzheimer’s Disease and Frail Syndrome: Features Overlap Predictive of Poor Outcome)
CNS & Neurological Disorders - Drug Targets The Relationships between the Transforming Growth Factor-β 1, Age and the Ultrasound Parameters of Arterial Wall
Vascular Disease Prevention (Discontinued) Organotypic Brain Slices of ADULT Transgenic Mice: A Tool to Study Alzheimer’s Disease
Current Alzheimer Research Graphical Abstracts
Protein & Peptide Letters 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 Evaluation of General Health Status in Diabetic Patients Using Short Form Health Survey (SF-36)
Current Diabetes Reviews Nanotechnology Advancements in the Diagnosis and Prevention of COVID-19: Past and Future
Coronaviruses Endothelial Dysfunction in Sepsis
Current Vascular Pharmacology Sodium Intake, Circulating Microvesicles and Cardiovascular Outcomes in Type 2 Diabetes
Current Diabetes Reviews Neuroprotection by Diazoxide in Animal Models for Cerebrovascular Disorders
Vascular Disease Prevention (Discontinued) Neuromuscular Disorders in Left Ventricular Hypertrabeculation/Noncompaction
Current Pharmaceutical Design Smoking, Estradiol Metabolism and Hormone Replacement Therapy
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Combination of Thiazide Diuretics and Angiotensin Receptor Blockers Attenuates Osteoporosis in Hypertensive Rats
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Sympathetic Overactivity in Patients with Chronic Renal Failure - The Culprit of Increased Cardiovascular Mortality?
Current Hypertension Reviews Hydroxamic Acids as Pharmacological Agents
Current Medicinal Chemistry Resilient Brain Aging: Characterization of Discordance between Alzheimer’s Disease Pathology and Cognition
Current Alzheimer Research