Anti-Obesity Drug Discovery and Development

Volume 3

by

Prof. Dr. Atta-ur-Rahman, Prof. Dr. M. Iqbal Choudhary

DOI: 10.2174/97816810818781170301
eISBN: 978-1-68108-187-8, 2017
ISBN: 978-1-68108-188-5
ISSN: 2467-9615 (Print)
ISSN: 2210-2698 (Online)



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Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic p...[view complete introduction]

Table of Contents

Preface

- Pp. i-ii (2)

Atta-ur Rahman and M. Iqbal Choudhary

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List of Contributors

- Pp. iii

Atta-ur Rahman and M. Iqbal Choudhary

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Current Status of Medical Therapy and New Targets for Anti-Obesity Drug Development

- Pp. 3-64 (62)

Chihiro Okuma, Yukihito Ishii and Takeshi Ohta

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Unravelling Potential Anorexigen Effects of Nesfatin-1: How Homeostatic Mechanisms Help Balance Excess Calories

- Pp. 65-79 (15)

Carmine Finelli

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Proteomics in the Characterization of New Target Therapies in Pediatric Obesity Treatment

- Pp. 80-148 (69)

Gillian E. Walker, Marilisa De Feudis, Marta Roccio, Gianni Bona and Flavia Prodam

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Relationship Between Hormonal Milieu and Oxidative Stress in Childhood Obesity: A Physiopathological Basis for Antioxidant Treatment and Prevention of Cardiovascular Risk

- Pp. 149-203 (55)

Antonio Mancini, Francesco Leo, Chantal Di Segni, Sebastiano Raimondo and Aurora Natalia Rossodivita

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The Role of Gut Microflora in Obesity - Does the Data Provide an Option for Intervention?

- Pp. 204-227 (24)

Parth J. Parekh, Edward C. Oldfield, Amrit Lamba and David A. Johnson

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Subject Index

- Pp. 228-235 (8)

Atta-ur Rahman and M. Iqbal Choudhary

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Preface

An epidemic of obesity is among the most important global healthcare challenges of the 21st century, causing considerable morbidity and mortality in a large segment of human population. Obesity has been identified as the largest preventable cause of numerous diseases. Obese and overweight population are at risk for a number of conditions, including high cholesterol levels, high blood pressure, heart diseases, diabetes, bone problems, skin diseases, neurological and psychological disorders, and increased chances of various malignancies. At individual level, obesity adversely effects the state of health and the quality of life, whereas at national level, it is a significant burden on the current healthcare systems. Unfortunately existing anti-obesity drugs are associated with numerous side effects, and are only prescribed when the benefits of treatment outweigh their risks.

The regulation of body weight is a complex process which involves cascades of mechanisms, including a variety of neuropeptides and transmitters in the brain, and endocrine and metabolic signalling molecules. Many of these processes are only superficially understood and extensive research is being conducted to decipher the complex biomolecular pathways behind the obesity syndrome. Understanding these inherent pathways, as well as the role of other factors, such as dietary habits, physical activities, gut microflora, etc. is critically important in devising successful strategies to combat obesity epidemics, including the discovery and development of improved treatments.

The 3rd volume of the book series entitled “Anti-Obesity Drug Discovery and Development” presents the most exciting recent developments in the field of obesity and its treatment. This book comprises five authoritative reviews ranging from identification of new drug targets to novel pharmacological and non-pharmacological interventions.

The first chapter by Ohta et al. presents a comprehensive account of recent literature on various treatment options available for obesity. Primary treatment of obesity disorder involves dietary restrictions, and exercise. However, in many cases, pharmacotherapy is imperative. The authors have categorised anti-obesity drugs into three classes, i.e. appetite suppressors, agents which inhibit nutritional absorptions, and drugs which accelerate energy expenditures. Various molecular targets in all three categories have been described, with merits and demerits of drugs developed against them.

Nesfatin-1 is a peptide which has attracted considerable attention as a possible antibody treatment of obesity. Nesfatin-1 is secreted by peripheral tissues, central and peripheral nervous system and it can pass the blood-brain barrier. It is involved in the regulation of energy homeostasis related with food regulation and water intake. It suppresses the urge for food independently from the leptin pathway and increases insulin secretion of the pancreatic beta islet cells. The use of Nesfatin-1 for the treatment of obesity has been widely investigated. Finelli has contributed a comprehensive review in chapter 2 on the potential of Nesfatin-1 as a new treatment for obesity and related disorders, its effects on other physiological parameters and the proposed mechanisms of action.

In chapter 3, Walker et al. focus on obesity in children, and identification of appropriate drug targets. Paediatric obesity is a growing menace with increasing prevalence globally. Overweight and obese children are at high risk of becoming overweight adolescents and adults, developing chronic diseases, such as heart disease and diabetes later in life. They are also more prone to develop stress, sadness, and low self-esteem. Adipose tissues (AT) play an important role in obesity. AT dysfunction leads to chronic inflammation, weight homeostasis, and insulin resistance. Understanding AT dysfunction at receptors and secondary messenger pathways is critically important in understanding the unique features of paediatric obesity at molecular levels. The authors have reviewed recent advances in the field of proteomics technologies with reference to their use in identifying key components of adipose proteome. This helps in understanding the pathogenesis of adipose tissue dysfunction in obesity

Mancini et al. have contributed a chapter on vascular, histopathological and metabolic changes that occur in obese children, which in many cases lead to metabolic syndrome, such as insulin resistance, type 2 diabetes, dyslipidemia, endothelial dysfunctions and cardiovascular disorders. The authors have focussed on the role of neuroendocrine peptides and cytokines in chronic inflammation and oxidative stress (OS). These mediators of chronic inflammation and OS are produced in adipose tissues, and are thus, directly responsible for endothelial dysfunction and insulin resistance. An extensive commentary on the role of oxidative stress in the onset of various obesity related diseases, such as atherogenesis and diabetes, is presented. Based on this, the authors have moved on to discuss the strategies to lower the chronic inflammation and oxidative stress in childhood obesity in order to prevent metabolic syndrome.

Gut microflora are perceived to play an important role in the prevention of various diseases, including obesity. Comparative studies have been conducted on bacterial flora of obese and lean individuals, and substantial differences were recorded. The disequilibrium in the composition of microorganisms that inhabit the human body can cause various diseases. High-throughput sequencing techniques and new tools used in bioinformatics have indicated strong relationships between the gut microbiota, and host's physiology. Disruption of the ecological equilibrium in the gut is called dysbiosis. Diet is a strong determinant of gut microbial balance. In chapter 5, Johnson et al. present a comprehensive discussion on state-of the-art understanding of the role of intestinal dysbiosis in the on-set of obesity disorder. They reviewed the most recent literature on the restoration of microflora in gut as a novel therapeutic option against the obesity epidemics. Strategies for the manipulation of intestinal microflora, such as antibiotic therapy against xenobiotic flora, supplementation of normal flora through probiotics and prebiotics and symbiotics (combination of probiotics and prebiotics), fecal microbiota transplant, etc. have been discussed. The role of intestinal microflora in metabolic programming is also extensively discussed.

In brief, the above cited reviews contributed by leading researchers in the field make this volume an interesting and useful reading for scientists and graduate students. We wish to express our felicitation and gratitude to all the authors for their excellent and scholarly contributions for the 3rd volume of this reputed series. We also greatly appreciate the efforts of the entire team of Bentham Science Publishers for efficient processing and timely management of the publication. The efforts of Ms. Faryal Sami (Assistant Manager Publications), Mr. Shehzad Naqvi (Senior Manager Publications) and the leadership of Mr. Mahmood Alam (Director Publications) are specially praiseworthy. We hope that like the previous volumes of this internationally recognized book series, the current compilation will also receive a wide readership and appreciation.

Prof. Dr. Atta-ur-Rahman FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

&

Prof. Dr. M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
International Center for Chemical and Biological Sciences
University of Karachi
Karachi
Pakistan

List of Contributors

Editor(s):
Prof. Dr. Atta-ur-Rahman
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK


Prof. Dr. M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
International Center for Chemical and Biological Sciences
University of Karachi
Karachi
Pakistan




Contributor(s):
Antonio Mancini
Departments of Medical Sciences and Pediatrics
Catholic University of the Sacred Heart
Rome
Italy


Aurora Natalia Rossodivita
Departments of Medical Sciences and Pediatrics
Catholic University of the Sacred Heart
Rome
Italy


Amrit Lamba
Department of Internal Medicine
Tulane University
New Orleans
LA
USA


Chantal Di Segni
Departments of Medical Sciences and Pediatrics
Catholic University of the Sacred Heart
Rome
Italy


Carmine Finelli
Department of Emergency and Internal Medicine
S. Maria della Pietà Nola’s Hospital, Via della Repubblica 1
80035 Nola (Na)
Italy


Chihiro Okuma
Central Pharmaceutical Research Institute
Japan Tobacco Inc.
Takatsuki
569-1125 Osaka
Japan


David A. Johnson
Department of Internal Medicine
Division of Gastroenterology and Hepatology, Eastern Virginia Medical School
Norfolk
VA
USA


Edward C. Oldfield
Department of Internal Medicine
Eastern Virginia Medical School
Norfolk
VA
USA


Francesco Leo
Departments of Medical Sciences and Pediatrics
Catholic University of the Sacred Heart
Rome
Italy


Flavia Prodam
Division of Pediatrics, Department of Health Sciences
Università Del Piemonte Orientale
Novara
Italy


Gianni Bona
Division of Pediatrics, Department of Health Sciences
Università Del Piemonte Orientale
Novara
Italy


Gillian E. Walker
Laboratory of Clinical Pediatrics, Department of Health Sciences
Università del Piemonte Orientale
Via Solaroli
Novara
Italy


Marilisa De Feudis
Laboratory of Clinical Pediatrics, Department of Health Sciences
Università del Piemonte Orientale
Via Solaroli
Novara
Italy


Marta Roccio
Laboratory of Clinical Pediatrics, Department of Health Sciences
Università del Piemonte Orientale
Via Solaroli
Novara
Italy


Parth J. Parekh
Department of Internal Medicine, Division of Gastroenterology and Hepatology
Tulane University
New Orleans
LA
USA


Sebastiano Raimondo
Departments of Medical Sciences and Pediatrics
Catholic University of the Sacred Heart
Rome
Italy


Takeshi Ohta
Central Pharmaceutical Research Institute
Japan Tobacco Inc.
Takatsuki
569-1125 Osaka
Japan


Yukihito Ishii
Central Pharmaceutical Research Institute
Japan Tobacco Inc.
Takatsuki
569-1125 Osaka
Japan




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