Adipotide Peptide – Potential in Diabetes Investigations


Adipotide FTPP peptide, also known as FTPP peptide, fat-targeted proapoptotic peptide, has been the subject of extensive research, including keeping diabetes under control. The results of these investigations have indicated a few possible properties, including:

• Enhanced insulin action

• Speeded-up weight loss among research models.

Peptides have recently gained attention because it has been suggested that they have multiple health properties and relatively few risks. Research suggests that Adipotide is a peptide specifically targeting adipose cells and may induce apoptosis (a.k.a. FTPP). Multiple experimental studies, some of which are detailed below, have examined the anti-obesity potential of Adipotide, a highly specific fat-burning peptide. Adipotide, as the name suggests, is a proapoptotic peptide that may cause fatty cells to self-destruct, as per studies.

Prohibitins are endogenous proteins that control processes like cell division, metabolism, and inflammation. Studies suggest that Adipotide is a prohibitin-targeting peptide that has speculated promise in several trials and scientific uses. [i] Dr. Wadih Arap, a Houston-based physician, and Renata Pasqualini, a scholar at the same cancer hospital and Dr. Arap's wife, independently found and studied Adipotide.

According to research, Adipotide, which was speculated to be an anti-cancer medication, seems to be encouraging results in reducing fat, leaving the pioneers "at a loss for words." It was hypothesized that [ii] cutting off the cancer cells' intake of oxygen and nutrients would kill them and slow their development. The peptide was hypothesized to have the same mode of action, but this time on adipose cells. Researchers found this intriguing and referred to the study as a "proof of concept," noting that more research into the peptide and its impacts on cells was needed. The cancer center partnered with Arrowhead Research Corporation to fund their studies, and the experts there established Ablaris Pharmaceuticals Inc. as a spinoff company. Further research was done on FTPP, hoping it would be the next great fat adjuvant. [ii]

Adipotide Peptide Overview

With the help of phage display technology, Kolonin and his team could identify and extract a naturally occurring peptide (sequence CKGGRAKDC), which they then fused with a proapoptotic sequence to create the now-named Adipotide molecule. White adipose tissue contains a peptide chain structurally similar to adiponectin, hence the name Adipotide. This finding and peptide properties suggest that the peptide may bind to and damage prohibitin PHB1 on the surface of fatty tissue, thereby disrupting blood flow to adipocytes (fat-forming cells). Studies suggest that Adipotide appears to recognize prohibitins, which function as an arterial sign of adipose regions and then trigger apoptosis or cell death. [iii]

Researchers thought that Adipotide would cause these fat cells to explode, which could be a reason for worry as it could lead to a fast flow of fat cells into the circulation, disrupting the metabolism and increasing hunger. Studies indicate that adipose cells may be used as an energy source by Adipotide. Thus, the most prevalent side effect of anti-obesity medications—a rise in appetite—appears not to have been a concern here. Therefore, this made the peptide interesting enough to warrant further study. Among the main hypothesized impacts of the studied peptide are (2)

• Weight reduction

• No detrimental effect on hunger.

• Lower levels of insulin intolerance

• Possible use in the context of cancer

Studies in primates used as a basis for early experimental research asserted that after being given Adipotide, the animals suggested seemingly elevated levels of insulin resistance. Therefore, Adipotide was proposed as a possible diagnostic and adjuvant option for type II diabetes. Research into the use of Adipotide in the context of cancer may be founded on the same principle as anti-cancer medicine, namely, the suppression of angiogenesis. Adipotide was tested in both fat and slender primates, but only the former reported weight loss due to presentation. This finding implied one of the many potential properties of this peptide: the molecule appeared to be extremely discriminating towards obese adipose regions only. [iv]

Adipotide Peptide and Cancer

Researchers analyzed the peptides and compounds found in various blood arteries and organs (both healthy and cancerous). Differential expression of proteins, peptides, and other molecular markers between normal and cancerous cells makes them attractive therapeutic targets. Different chemical separation and analysis methods identified four native ligand receptors unique to cancerous cells. Research purports that some highly specific peptides, such as Adipotide, may be extremely helpful in attenuating the action of these receptors, thereby suggesting their promise in the context of cancer. [v]

Adipotide Peptide and Diabetes

Adipotide peptide was given to obese rodents to learn more about its potential impact and process on fat cells. Surprisingly, it was speculated that within 2–3 days of presentation, the rodents appeared to show signs of better glucose tolerance and reduced amounts of blood lipids. These modifications have been theorized to occur before the weight reduction caused by the peptide. This research provided preliminary data for the peptide's application in diabetes. Research suggests that since apoptosis is Adipotide's primary mechanism of action, it was originally thought that the peptide would impede the operation of the arterial system due to harm to the vascular cells. Adipotide appears to decrease adipose tissue cell bulk, and it has also been proposed that it may improve its working, which would account for enhanced hormone release and gene expression. [vi]

Studies Using Adipotide Peptide

Clinical studies of Adipotide were revealed for 2011-2012 after experts reviewed positive findings in mice and primates. Part I of the clinical study was created for subjects with prostate cancer who were not receiving any extra therapy. The plan called for the study to last 28 days, during which Adipotide would be given once daily. [vii] This peptide is still in the early stages of research, but some trials have been halted as of 2019.

References

[i] Thuaud, F., Ribeiro, N., Nebigil, C. G., & Désaubry, L. (2013). Prohibitin ligands in cell death and survival: mode of action and therapeutic potential. Chemistry & biology, 20(3), 316–331. https://doi.org/10.1016/j.chembiol.2013.02.006

[ii] Melissa H., Cancer treatment shows promise for rapid weight loss, Los Angeles Times, 10 Nov 2011. https://www.latimes.com/local/la-xpm-2011-nov-10-la-he-drug-fat-loss-20111110-story.html

[iii] Kolonin, Mikhail G et al. “Reversal of obesity by targeted ablation of adipose tissue.” Nature medicine vol. 10,6 (2004): 625-32. https://pubmed.ncbi.nlm.nih.gov/15133506/

[iv] Experimental Drug Slims Obese Monkeys https://www.medicinenet.com/script/main/art.asp?articlekey=151452

[v] Staquicini, Fernanda I et al. “Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients.” Proceedings of the National Academy of Sciences of the United States of America vol. 108,46 (2011): 18637-42. doi:10.1073/pnas.1114503108. https://pubmed.ncbi.nlm.nih.gov/22049339/

[vi] Kim, Dong-Hoon et al. “Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.” Diabetes vol. 61,9 (2012): 2299-310. doi:10.2337/db11-1579. https://pubmed.ncbi.nlm.nih.gov/22733798/

[vii] Arrowhead Announces Dosing of First Patient with Anti-Obesity Treatment Adipotide® in a Phase 1 Clinical Trial, 11 Jul 2012. https://www.businesswire.com/news/home/20120711005485/en/

 

 

 

  

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