Peptides and Peptidomimetics as Potential Antiobesity Agents: Overview of Current Status

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.

The Essentials of Marine Biotechnology

“…The increasing standard of life inherently represents a growing demand for pharmaceuticals, nutraceuticals and cosmeceuticals. Marine organisms, such as algae, sponges, mollusks (including cone snails), cyanobacteria, actinobacteria, fungi, tunicates and fish biosynthesize metabolites with significant biological activities for therapeutic and industrial applications, with anticancer, anti-inflammatory, anti-and pro-osteogenic, antiobesity, antimicrobial, antiviral, and anticoagulant activities (Majik et al, 2014;Surget et al, 2017;Carson et al, 2018a,b;Jin Q. et al, 2018;Kumar, 2019;Mayer et al, 2020). To date, seventeen clinically approved drugs of marine origin include: cytarabine (Cytosar-U R ), nelarabine (Arranon R ), fludarabine phosphate (Fludara R ), trabectedin (Yondelis R ), eribulin mesylate (Halaven R ), brentuximab vedotin (Adcetris R ), plitidepsin (Aplidin R ), polatuzumab vedotin (Polivy TM ), enfortumab vedotin-ejfv (PADCEV TM ), and more recently, lurbinectedin (Zepzelca R ) and belantamab mafodotin (BLENREP R ) for cancer treatment, ziconotide (Prialt R ) for severe chronic pain, ω-3acid ethyl esters (Lovaza R ), eicosapentaenoic acid ethyl ester (Vascepa R ), and ω-3-carboxylic esters (Epanova R ) for hypertriglyceridemia treatment, and ι-carrageenan (carragelose) and vidarabine (Vira-A R ; US discontinued 17 ) for antiviral treatment (Martins et al, 2014;Jimenez et al, 2020).…”

The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

“…The lipolysis of adipose tissue is a catabolic process stimulated by the adrenergic system that leads to the breakdown of triglycerides stored in adipose cells releasing fatty acids and glycerol. The dysregulation of the processes that are involved in lipolysis has already been observed in obesity [92,93]. To evaluate whether the lipolytic pathway of THOP1 −/− animals was altered, a glycerol dosage test was performed.…”

Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions

“…Therefore, if InPeps from 2SCP-2 that were found to have their levels altered in THOP1 −/− could interfere with lipid composition and/or the association of proteins to adipose tissue lipid vesicles, also energy metabolism and fat deposition could be affected. Similarly, InPeps from apolipoprotein A could possess anti-obesity functions [ 145 ]. Acyl-CoA-binding protein (ACBP; also known as diazepam-binding inhibitor, DBI) is a lipogenic factor that triggers food intake and obesity [ 146 ].…”