Anti-obesity Drug Discovery and Development: Volume 4

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

• Publisher: Bentham Science Publishers
• Year: 2018
• Print ISBN:
  9781681085593
• eBook ISBN:
  9781681085586
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic predisposition, endocrine disorders, medications and psychiatric illnesses. The incidence of obesity among populations in

Multi Targeted Strategies Towards Identification of Potential Drug Candidates from Natural Products in the Management of Obesity

Baddireddi Subhadra Lakshmi^{*, 1, 2}, Gopal Thiyagarajan²

¹ Centre for Food Technology, Anna University, Chennai, India

² Department of Biotechnology, Anna University, Chennai, India

Abstract

Obesity, a chronic metabolic disorder, is caused by an imbalance between energy intake and expenditure, and has been associated with insulin resistance, Type 2 Diabetes Mellitus (T2DM), hypertension, myocardial infarction, fatty liver disease, stroke, osteoarthritis and certain cancers. Currently, drugs used for the management of obesity like orlistat (lipase inhibitor) and Phentermine (norepinephrine and dopamine releasing agent) have been reported to exhibit adverse side effects.

Recent advancements in the understanding of biological systems have opened up new possibilities towards a multi targeted approach, designed to target more than one biological mechanism that might ultimately be more effective in producing sustained weight loss along with improvement in comorbidities. Multi-targeted drugs have emerged as a new paradigm in the last decade owing to their advantages in the treatment of complex multifactorial diseases such as obesity and T2DM. Most recently, glucagon-like peptide-1 (GLP-1) mimetics and insulin secretagogues have been reported for their anti-obesity activity, due to their property of delaying the rate of gastric emptying and appetite suppression in CNS, thus promoting satiety and weight loss.

Medicinal plants have been established as rich resources for the identification of potential drug candidates. Most of these isolated natural products exhibit multi-targeted action owing to their diverse and complex structure. Numerous natural bioactive molecules including polyphenols, alkaloids, sterols, glycosides, terpenes and saponins have been identified as potential drug candidates for the management of obesity. Cellular and molecular studies have shown that these natural products suppress appetite and reduce food intake, reduce intestinal absorption of fats, attenuate lipid synthesis and accumulation, stimulate lipolysis, promote oxidation of fatty acids and reduce inflammation.

This chapter will focus on the molecular targets and mechanisms involved in weight regulation, provide an insight into the isolation of bioactive compounds from medicinal plants, and the multi targeted strategies for the control of obesity.

Keywords: Adiponectin, Adipogenesis, Allosteric PTP1B inhibitor, Antiobesity drugs, Appetite suppressors, AMPK, β-oxidation, C/EBP, Cholecystokinin agonists, DPP4, GLP1, HSL, Leptin, Lipolysis, Multi targeted drugs, Natural products, Neuropeptide Y antagonist, Obesity, Pancreatic lipase, Partial PPARγ agonist, PPARα, Sirtuins, SREBP, Thermogenesis, UCPs.

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^* Corresponding author Baddireddi Subhadra Lakshmi: Centre for Food Technology, Department of Biotechnology, Anna University, Chennai – 600 025, Tamil Nadu, India; Tel: [phone]; Fax: [phone]; E-mail: [email protected],

INTRODUCTION

Obesity, characterized by surplus of fat mass, is increasing owing to increased consumption of calorically rich diet and lack of physical activity. Obesity occurs when the intake of energy surpasses expenditure, triggering an overgrowth of adipocytes. Epidemiologically, excess of visceral fat, as determined by the waist to hip ratio, has been associated with metabolic disorders [1]. According to the World Health Organization (WHO), a person with BMI (body mass index) greater than 25 Kg/m² is overweight, a BMI greater than 30 Kg/m² is categorized as obese, while a BMI value ≥40 Kg/m² is designated as “morbidly obese”.

Obesity is a serious public health concern affecting people all around the world. Globally, the epidemic of obesity is growing rapidly with almost 600 million adults characterized to be obese and around 1.9 million adults (> 18 years) observed to be overweight. The reasons for weight gain could be either due to intrinsic or extrinsic factors. The intrinsic factors include genetic predisposition, epigenetic or endocrine disturbances, while extrinsic factors include increased consumption of high energy-dense foods, limited physical activity and a sedentary life style [2, 3].

Metabolic syndrome is characterized by a coexistence of multiple risk factors, with central obesity being a cardinal feature [4]. The pathogenesis of metabolic syndrome is closely related to alterations in lipogenesis, utilization of fatty acids and energy expenditure. Eventually, these changes affect the storage of lipids in ectopic tissues such as intraperitoneal, skeletal and liver depots, leading to the progression of other complications including insulin resistance, diabetes, dyslipidemia, hypertension, stroke, osteoarthritis, gout, gallbladder disease, pulmonary and cardio vascular diseases [5]. A principal contributor in the progression of obesity is hyperinsulinemia, wherein elevated levels of cellular triacylglycerol and alterations in lipid and glucose metabolism are observed [6].

CURRENT TREATMENT STRATEGIES FOR OBESITY

Although diet and exercise are lifestyle modifications often prescribed for the control of obesity, they usually fail to produce sustainable weight loss [7]. Bariatric surgery has been shown to be a more effective way to reduce weight and decrease comorbidities [8]. However, due to surgical risks, bariatric surgery is reserved for persons who are morbidly obese [9].

Besides surgery and lifestyle modification, therapeutic strategies for the control of...

Table of contents

• Welcome
• Table of Contents
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• List of Contributors
• Dietary Modulation, Obesity and Cancer Prevention
• The Role of Anti-Obesity Medications in Polycystic Ovary Syndrome
• Sirtuins and Bile Acids: Potential Anti-obesity Strategies Targeting Mitochondria
• Development and Characterization of Calcium Silicate Based Formulations for Anti-Obesity Therapy: Orlistat
• Multi Targeted Strategies Towards Identification of Potential Drug Candidates from Natural Products in the Management of Obesity
• Anti-Obesity Molecules from Plants and their Mode of Action