Adipotide FTPP Research
ADIPOTIDE FTPP MECHANISM OF ACTION
Adipotide has been suggested to exert action by binding to the receptors for two specific proteins, ANXA2 (Annexin A2) and prohibitin (PHB). It appears that these receptors may be expressed in a wide range of cells, but immunohistochemical analysis hypothesizes that they potentially form a unique ANXA2-prohibitin receptor system that are apparently found in white fat tissue.[2] It appears that these receptors were found on the endothelial cells of blood vessels that support white fat cells. Furthermore, research suggests that these receptors may play a role in regulating fatty acid transport in white adipose tissues (WAT).[3] To potentially explore this notion, the researchers disrupted the binding between ANXA2 and prohibitin genetically or by utilizing a blocking peptide. Their findings seem to indicate that the efficiency of fatty acid transport might depend on the interaction between ANXA2 and prohibitin. Moreover, the study suggests that the interaction between ANXA2 and prohibitin may facilitate the transport of fatty acids from the endothelium into adipocytes. The researchers also stumbled upon the revelation that ANXA2 and prohibitin form a complex alongside the fatty acid transporter CD36.
This intricate connection involving ANXA2, prohibitin, and CD36 potentially plays a role in mediating fatty acid transport in white adipose tissues. Furthermore, the researchers noticed that the coexistence of prohibitin and CD36 on the surface of adipocytes appears to be induced by extracellular fatty acids. This lead them to the hypothesis that the presence of fatty acids in the external environment may trigger the interaction between prohibitin and CD36 on the adipocyte surface. Hypothetically, inhibiting the ANXA2 protein may lead to hypertrophy of white adipose cells due to reduced uptake of fatty acids. On the other hand, prohibitin is a multifunctional membrane-associated protein that may be thought to regulate cell survival and growth. By shuttling from the cell’s membrane to its nucleus, it may hypothetically trigger apoptosis. Thus, the scientists commented that “suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases.”
ADIPOTIDE FTPP STRUCTURE
Adipotide appears to have a unique structure consisting of the amino acid sequence GKGGRAKDC-GG-D(KLAKLAK)2. The nine amino acid sequence CKGGRAKDC may exhibit a specific affinity to the ANXA2-prohibitin receptor system found in the blood vessels supporting white adipose cells.[4] The researchers utilized phage display, a technique that is considered to enable the identification of specific peptide motifs, to isolate a peptide sequence CKGGRAKDC. Moreover, the CKGGRAKDC peptide appears to associate with a membrane protein called prohibitin, which has been identified as a potential vascular marker of adipose tissue. By directing a proapoptotic peptide towards prohibitin in the adipose vasculature, the researchers induced the ablation (removal) of white fat. This resulted in the possible resorption of established white adipose tissue and the potential normalization of metabolism. As a consequence, rapid obesity reversal was reported to be achieved. It is suggested that prohibitin is expressed in the blood vessels of white fat. However, it is crucial to note that the study solely focuses on elucidating the mechanisms involved and did not provide any definitive suggestions or implications regarding its potential.
At the same time, (KLAKLAK)2 may disrupt mitochondrial membranes upon receptor-mediated cell internalization and possibly cause programmed cell death. As Adipotide may bind to prohibitin in white adipose vasculature, it potentially triggers apoptosis and hypothetically results in the ablation of white fat cells. According to research, Adipotide and other similar peptidomimetics may hold potential for reducing both subcutaneous and visceral fat and may even target intra-organ fat, such as in fatty liver.[5] In fact, the researchers posit that “vascular-targeted nanotherapy has the potential to contribute to the control of adipose function and ectopic fat deposition associated with obesity and the metabolic syndrome.”
