Neuropeptides In Amylin & Appetite Regulation And Obesity- A Review Of Resolutions And Treatments Of Obesity

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Acknowledgement

I would take this opportunity to thank my research supervisor, family and friends for their support and guidance without which this research would not have been possible.

Declaration

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Abstract

Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.

Table of Contents

ACKNOWLEDGEMENTII

DECLARATIONIII

ABSTRACTIV

CHAPTER 1: INTRODUCTION1

CHAPTER 2: OREXIGENIC NEUROPEPTIDES SECRETED BY HYPOTHALAMUS7

CHAPTER 3: ANORECTIC NEUROPEPTIDES SECRETED BY HYPOTHALAMUS19

CHAPTER 4: CASE STUDIES30

CHAPTER 5: DISCUSSION & CONCLUSION77

REFERENCES97

Chapter 1: Introduction

Obesity is a serious medical condition whose prevalence is increasing in developing countries also. This growing incidence represents a pandemic that needs urgent attention if the potential morbidity, mortality, and economic tolls that will be left in its wake are to be avoided. Obesity predisposes to increased risk of a number of medical conditions including type II diabetes mellitus, hypertension, coronary heart disease, osteoarthritis, respiratory problems and cancers of breast, endometrium, prostate, bowel cancers (Neary et al., 2007).

Obesity represents a state of excess storage of body fat. Although very similar, the term overweight is defined as an excess body weight for height. The body mass index (BMI), also known as the Quetelet index is a WHO accepted index for classifying the degree of obesity. Standards defining overweight and obesity on the basis of ...