Adipotide, aka FTPP or Fat Targeted Proapoptotic Peptide, is a synthetically developed peptidomimetic compound containing pro-apoptotic elements. Adipotide was developed to inhibit the proliferation of cancer cells through starvation. Research has suggested the impact of the peptide in depriving adipocytes of blood supply, causing them to die and be reabsorbed.
Adipotide has also been researched for its action in metabolic function, with initial studies performed on monkeys and rodents. According to the results, rodents presented a 30% reduction in body weight. After 4 weeks of daily administration of adipotide and 4 weeks of no treatment, ten rhesus, obese females had a 39% decrease in fat deposits and 11% reduction in body weight, on average. Researchers continue to consider Adipotide for its potential as a metabolic agent. This is due to the reported death of fat cells and the reduction of adipose tissue beneath the skin in initial studies. As a result of the reduced adipose tissue, waist circumference, and overall BMI are reduced.
Adipotide is a synthetic working compound with the potential to mitigate adipocytes and reduce an the overall concentration of subcutaneous fat through inducing the termination of cells that supply adipocytes within the blood vessels. R. Pasqualini and Dr. W. Arap are responsible for creating Adipotide. They reported that Adipotide appeared to deprive adipocytes in the blood, causing their death and reabsorption in the body. Research in the peptide is still in trial phases and is being tested on animals using clinical studies.
Adipotide Peptide Research
Research suggests this peptide acts through the discriminatory killing of cells in the blood vessels that feed white adipose tissue. Adipotide may lead to the vessels’ shrinkage (atrophy) and inevitably the death of cells (apoptosis), thus, cutting off the blood supply to adipocytes. This, then, may lead to insufficient or no oxygen and blood supply (ischemic injury) to the adipocytes. Since the impact is not reversible, the death of fat cells is also inevitable.
The stereo-chemical structure of this peptide, as presented by molecular analysis, has displayed the potential of Adipotide to bind to 2 particular receptors that are found solely in the blood vessels that feed white adipose tissue. ANXA-2 and Prohibitin are the particular receptors just mentioned. Because of these receptors’ tissue specificity, the peptide has no reported effect on brown adipose tissue, and may not impact the thermogenesis of adaptive, brown fat. The thermogenesis of brown fat is particularly important for babies, as they don’t have a large capacity for heat conservation since the ratio of the body’s surface area to its volume prefers higher levels of heat loss. White adipose tissue is only produced when consumed energy surpasses used energy.
Epidemiological studies suggested that nearly 34% of the total American adult population is affected by obesity, which is caused by too much adipose tissue mass. Research has also shown that white adipose tissue is the primary contributor to the obesity of the population. Body weight increases do not necessarily have to do with obesity, because such increases may result from increases in lean body mass and not exactly from fat cell increase. Obesity is also linked to and contributes to a rise in co-morbidity and mortality rates.
BMI Obesity and Adiposity
As of now, obesity is assessed using the skinfold thickness (anthropometry), Body Mass Index (BMI), and densitometry. A BMI score of thirty (30) is set as the obesity threshold. A rise in adiposity puts impacted individuals at high risk for a variety of health issues, such as hyperlipidemia, cancers, hypertension, Non-Insulin Dependent Diabetes Mellitus (NIDDM), metabolic syndrome, myocardial infarction, and cerebrovascular accidents. The morbidity rate is determined by how the adipose tissue is distributed; for example, adiposity localized to the buttocks and lower limbs is far less dangerous than adiposity concentrated in the abdominal region, leading to greater morbidity. For these reasons, the waist-to-hip ratio is clinically used to determine the chances of an individual developing one or more of the mentioned health conditions. The link between the rise in morbidity and abdominal adiposity is assigned to the knowledge that fat cells within the abdomen have more lipolytic activity than the fat cells of the lower limbs.
What Is Adipose Tissue?
Adipose tissue is made up of lipid-storing adipose cells (adipocytes), and the vascular section where preadipocytes and macrophages are found. Adipose cell hypertrophy results from an increase of lipid discharge, and the rise in adipose mass is caused by the subsequent hyperplasia of adipose cells. This increase is marked by an elevated differentiation of preadipocytes to adipocytes, as well as a large amount of invading macrophages. Such a transformation and maintenance of elevated adipose mass is held up by a constant blood supply to the fat tissue.
What Is Ischemic Injury?
Ischemic injury – the lack of oxygen and blood supply to the adipose tissue – would prevent the transformation and encourage the death of those injured fat cells. That’s why a peptidomimetic like adipotide would lead to a decrease in adipose mass by producing ischemic injury (that is not reversible) to the fat cells in white adipose tissue.
Adipotide Peptide and Obesity Research
A study was conducted by M G Kolonin et al (2004) [1] with the purpose of presenting that a targeted triggering of cell death in the blood vessels’ white adipose tissue could be utilized as a therapy towards obesity. The study used mice as its test subjects. The experiment used a peptide motif isolate whose sequence allowed it to discriminatorily target white adipose tissue vasculature. In living organisms, phage display was utilized to separate the peptide motif so that it’s alone. The results of the study suggested that the peptide motif is linked with prohibitin, a multifunctional membrane protein. It was suggested that prohibitin was a label of vascular white adipose tissue. Also indicated by the results was the hypothesis that the cell death-causing peptide’s targeting of white adipose tissue vasculature led to the removal of the adipose tissue mass. The reabsorption of the white adipose led to a regularization of the metabolic processes altogether. This regulation took place without any reported significant side effects. Monkeys and rodents are biologically different, and this leads to major difficulties in the translation of obesity treatments developed in rats into those for humans. Such challenges would be decreased if test subjects were also primates themselves.
Adipotide Peptide and Weight Loss
A team of researchers conducted a study (2011) [3] in which a ligand-directed peptidomimetic was assessed for its functions in monkeys with obesity. The ligand-directed peptidomimetic was also named Adipotide. The study’s results presented that Adipotide did appear to trigger cell death in white adipose tissue vasculature, resulting in an improved insulin function and an accelerated decrease in weight in the primates.
The decrease in white fat mass was supported by dual-energy x-ray absorptiometry (DEXA) and Magnetic resonance imaging (MRI). Results displayed an apparent enhancement in the primates’ renal function. The research suggested that Adipotide peptide may have potential in obesity treatment prototypes.
In another study in 2011 [2] in which vascular labels for various organs were assessed, the research involved filtering of the library of peptides in patients with cancer, with the goal of discovering ligand-receptors particularly for specific vascular beds. A survey of motifs stemming from biopsies yielded a non-random dispersion pattern which implied the possibility to target particular, systemic vascular beds. Deeper analysis through affinity chromatography , similarity search, and protein arrays uncovered four native ligand-receptors. Two native ligand-receptors were dispersed in multiple tissues. The other receptors displayed a restricted particular dispersion with RAGE/leukocyte proteinase-3 being held to the development of secondary malignant growth in the bone, and prohibitin/annexin A2 being held to white adipose tissue. This study indicated that the receptors expressed in the white fat vasculature of are prohibitin and ANXA-2 (annexin A2).
Adipotide Peptide Safety Profile
Although the first batch of trials have been successfully performed on monkeys and rodents, researchers have observed some adverse side effects. A report included apparent wounds in the small kidney that could lead to kidney failure if left untreated. The other noted side effect was dehydration. The peptide has not been researched sufficiently to establish a safety profile.
Researchers can find Adipotide and other high quality peptides for research by visiting Core Peptides. The peptide is available strictly for research and laboratory use, and is not approved for human usage.
Adipotide peptide (10mg) vial – Core Peptides
References:
- Kolonin, M. G., Saha, P. K., Chan, L., Pasqualini, R., & Arap, W. Reversal of obesity by targeted ablation of adipose tissue. Nature medicine, 2004.
- Staquicini, F. I., Cardó-Vila, M., Kolonin, M. G., … & Arap, W. Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. Proceedings of the National Academy of Sciences, 2011.
- Barnhart, K. F., Christianson, D. R., Hanley, P. W., … & Pasqualini, R. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Science translational medicine, 2011.
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Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.