Abstract

There is a high occurrence of obesity worldwide without many new medications being approved for its treatment. Therefore, there is an urgent need to introduce new approaches for treating obesity. Bioactive peptides have been used to treat metabolic disorders- such as type-2 diabetes and obesity; while also possessing anti-oxidant, anti-inflammatory, anti-microbial, and anti-viral properties. However, the development of these peptides has taken backstage due to their size, reduced stability, poor delivery and bioavailability, fast rate of degradation etc. But with the emergence of newer techniques for multifunctional peptides, mimetics, peptide analogs, and aptamers, there is a sudden revival in this therapeutic field. An increased attention is required for development of the natural peptides from food and marine sources which can mimic the function of mediators involved in weight management to avoid obesity. Herein, the search for the structures of anti-obesity peptides was carried out in order to establish their potential for drug development in future. An extensive search for the current status of endogenous, food and marine peptides, with reference to novel and interesting experimental approaches based on peptidomimetics for controlling obesity, was performed. Apolipoprotein A-I (apoA-I), melanocortin-4 receptor (MC4R)-specific agonist, GLP-1 dual and triple agonists, neuropeptides and prolactin-releasing peptide mimetics were specifically examined for their anti-obesity role. Novel peptides, mimetics, and synthesis interventions are transpiring and might offer safer alternatives for otherwise scarcely available safe antiobesity drug. A deeper understanding of peptides and their chemistry through the use of peptide engineering can be useful to overcome the disadvantages and select best mimetics and analogs for treatment in future.

Highlights

  • Obesity is an abnormal condition which involves accumulation of excessive body fat and increases the risk of associated health problems

  • The secretion of brain-derived neurotrophic factor (BDNF) leads to its interaction with trkB situated in the paraventricular nucleus (PVN), dorsomedial hypothalamus (DMH), Arcuate nucleus (Arc) and ventromedial hypothalamus (VMH), causing reduced food intake by stimulating the feedback mechanism

  • Leptin is responsible for causing direct activation of phosphoinositide 3-kinase (PI3K) in pro-opiomelanocortin (POMC) neurons while generating an inactivation in Agouti-related protein (AgRP) neurons [17]

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Summary

INTRODUCTION

Obesity is an abnormal condition which involves accumulation of excessive body fat and increases the risk of associated health problems. An increase in glucocorticoid levels are observed in MCH-deficient mice, demonstrating the importance of MCHR1 in adrenal functions [24] Orexins perform their actions through the ventral posterior Arc where actuation of OX2R orexin receptors empowers a Na+/Ca2+ trade current in GABAergic neurons and causing depolarization and enhancing the firing rate in the cells [25]. When engineering a new “Two-in-one” peptide, Day et al [44] introduced a cyclic amide function in the peptide chain to make the complex more stable, and locked a huge polyethylene glycol group to prevent its filtration from the kidney These prudent modifications in the peptide exhibited full potency at both the glucagon and GLP receptor and caused dramatic weight loss in obese mice. D’Amato et al [47] conducted an experiment in a small group of patients and could conclude

Leptin receptor
Apolipoprotein Mimetic Peptides
Mechanism of action
Lipolysis of adipose tissue
FOOD PEPTIDES
MARINE PEPTIDES
Findings
CONCLUSION AND FUTURE DIRECTIONS
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