Adipotide or FTPP (Fat Targeted Proapoptotic Peptide), possible treatment of obesity and weight loss! -By Polypeptide.ltd
Authoritative source：PubChem
Introduction Adipotide, also known as FTPP (Fat Targeted Proapoptotic Peptide), is a research peptide intended for use as a possible therapy for obesity. In order to reduce fat mass and address concerns connected to obesity, it seeks to trigger apoptosis in fat cells, specifically in white adipose tissue.
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Adipotide affects fatty acid transport and cell functions by attaching to ANXA2 and prohibitin receptors on blood arteries supporting white adipose tissue. Its unique structural features, which include stretches like GKGGRAKDC-GG-D(KLAKLAK)2, make it possible to interact with these receptors. Adipotide damages the mitochondria of fat cells after binding, leading to programmed cell death. This method of gradually eliminating fat cells holds promise for reducing visceral and subcutaneous fat, as well as for reducing accumulation of fat in tissues and organs like the fatty liver.
How Does Adipotide Peptide Work? ① Receptor Binding: Adipotide ’ s distinctive structure, which comprises particular amino acid sequences, is intended to bind to receptors. The peptide can attach to receptors on the outside of blood arteries that support white adipose tissue thanks to these sequences. It primarily targets prohibitin and ANXA2 (annexin A2). ②Receptor Interaction: Adipotide interacts with the prohibitin and ANXA2 receptors, which leads to the onset of a chain of cellular processes. In white adipose tissue, prohibitin and ANXA2 are involved in cellular functions and fatty acid transport. ③ Mitochondrial Disruption: The structure of adipotide comprises sequences that enable it to disassemble the mitochondria in fat cells. The organelles in cells that produce energy are called mitochondria. Adipotide’s interference results in mitochondrial malfunction and damage.
④Apoptosis: Apoptosis, or programmed cell death, occurs in fat cells as a result of adipotide’s disruption of the mitochondria and the cellular stress it causes. Cells naturally purge damaged or undesirable cells from the body through this procedure. ⑤Fat Cell Elimination: Over time, the quantity of white adipose tissue diminishes as more fat cells are exposed to adipotide and experience apoptosis. This may result in less fat building up in the
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body’s intended target locations.
Adipotide Peptide and Weight Loss Adipotide is a relatively recent development in the field of weight loss and metabolic research. It is a synthetic proapoptotic peptide that was developed in the early 21st century. Clinical trials were conducted on Rhesus monkeys, which are considered relevant primate models for human obesity in 2011 during Phase 1 trials. Female monkeys were selected based on their history of spontaneous obesity and Adipotide was administered through daily subcutaneous injections. ①Animal Studies on Rhesus Monkeys: Daily subcutaneous treatment with increasing doses of adipotide led to dose-dependent decreases in body weight, body mass index (BMI), and abdominal circumference. After 9 weeks of dosing, treated monkeys showed a weight loss of 15.4% to 20.4%, a decrease in BMI of 17.1% to 20.4%, and a reduction in abdominal circumferences by 13.1% to 14.2%. Adipotide-treated monkeys exhibited improved insulin sensitivity, as indicated by reduced insulinogenic index (a measure of insulin resistance) by 48.5%. Adipotide treatment did not cause significant changes in serum lipid profiles or liver enzymes. There was evidence of mild and reversible renal toxicity, including alterations in serum creatinine, serum phosphorus, serum potassium, and urinary parameters. However, these changes reversed after discontinuation of treatment. ②Weight Loss and Metabolic Benefits: Adipotide led to marked weight loss primarily due to the reduction in visceral (abdominal) fat. Improved insulin sensitivity and reduced insulin resistance were observed in treated monkeys. Serum-free fatty acids decreased over the treatment period, suggesting improved fat metabolism. ③Specificity and Safety: Adipotide demonstrated tissue specificity by targeting receptors on the endothelium of blood vessels supplying white adipose tissue. The side effects were generally mild and reversible, primarily involving renal toxicity and mild dehydration.
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There were no significant adverse effects on critical organs or neurotransmitter function. ④Conclusion: The research on Adipotide indicates that it can induce rapid weight loss through targeted apoptosis of fat cells. This effect is achieved by binding to specific receptors on blood vessel endothelial cells, leading to fat cell death and subsequent reduction in fat tissue volume. Adipotide showed promise in reducing body weight, improving insulin sensitivity, and demonstrating tissue specificity in nonhuman primate models of obesity. However, there were also mild and reversible renal toxicity and altered urinary parameters associated with treatment. Please note that while the data presented here provides insights into the effects of Adipotide, further research and clinical trials are necessary to fully understand its potential for weight loss and its safety profile in humans.
Reference citations [1]Barnhart, K. F., Christianson, D. R., Hanley, P. W., … & Pasqualini, R. A peptidomimetic targeting white fat causes weight loss and improved insulin translational medicine, 2011.
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[2]Thuaud F, Ribeiro N, Nebigil CG, Désaubry L. Prohibitin ligands in cell death and survival: mode of action and therapeutic potential. Chem Biol. 2013;20(3):316-331. [3] Daquinag AC, Tseng C, Salameh A, et al. Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity development. Cell Death Differ. 2015;22(2):351-363. [4]Kim DH, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, Newgard CB, Woods SC, Seeley RJ. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012 Sep;61(9):2299-310. [5]Smith, T. L., Sidman, R. L., Arap, W., & Pasqualini, R. (2022). Targeting vascular zip codes: from combinatorial selection to drug prototypes. In The Vasculome (pp. 393-401). Academic Press.
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[6]Blaszczak AM, Jalilvand A, Hsueh WA. Adipocytes, Innate Immunity and Obesity: A Mini-Review. Front Immunol. 2021;12:650768. Published 2021 Jun 24. [7]Staquicini FI, Cardó-Vila M, Kolonin MG, Trepel M, Edwards JK, Nunes DN, Sergeeva A, Efstathiou E, Sun J, Almeida NF, Tu SM, Botz GH, Wallace MJ, O’Connell DJ, Krajewski S, Gershenwald JE, Molldrem JJ, Flamm AL, Koivunen E, Pentz RD, Dias-Neto E, Setubal JC, Cahill DJ, Troncoso P, Do KA, Logothetis CJ, Sidman RL, Pasqualini R, Arap W. Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18637-42. [8]Hossen N, Kajimoto K, Akita H, Hyodo M, Harashima H. A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication. J Control Release. 2013;171(2):104-112. [9]Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004 Jun;10(6):625-32. [10]Salameh A, Daquinag AC, Staquicini DI, An Z, Hajjar KA, Pasqualini R, Arap W, Kolonin MG. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue. JCI Insight. 2016 Jul 7;1(10):e86351. [11]Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. [12]Fang Y, Kaszuba T, Imoukhuede PI. Systems Biology Will Direct Vascular-Targeted Therapy for Obesity. Front Physiol. 2020;11:831. Published 2020 Jul 15. [13]Kim DH, Woods SC, Seeley RJ. Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight. Diabetes. 2010 Apr;59(4):907-15. [14]”Prohibitin-targeting peptide 1″. NCI Drug Dictionary. National Cancer Institutes. 2 February 2011. [15]”Blood vessel mapping reveals four new ‘ZIP codes'”. medicalxpress. 24 October 2011. Retrieved 10 November 2011.
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Author of this article: Dr. Jean Zeng graduated from king’s college london Faculty of Life Sciences & Medicine. Scientific Journal paper Author: 1.Kirstin F. Barnhart Department of Veterinary Science and Keeling Center for Comparative Medicine and Research, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. 2.Dong-Hoon Kim Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea 3.Dr David Preiss MRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK 4.Rae-Chi Huang Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia, Australia 5.Frédéric Thuaud Therapeutic Innovation Laboratory (UMR 7200), CNRS/Université de Strasbourg, Faculté de Pharmacie, France In no way does this doctor/scientist endorse or advocate the purchase, sale, or use of this product for any reason. Polypeptide.ltd has no affiliation or relationship, implied or otherwise, with this physician. The purpose of citing this doctor is to acknowledge, acknowledge and commend the exhaustive research and development work done by the scientists working on this peptide. Author of this article: Dr. Jean Zeng graduated from king's college london Faculty of Life Sciences & Medicine. Scientific Journal paper Author: Stephen C. Bain Diabetes Research Group, Swansea University Medical School, Swansea, SA2 8PP, UK
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Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, SA2 8QA, UK In no way does this doctor/scientist endorse or advocate the purchase, sale, or use of this product for any reason. Polypeptide.ltd has no affiliation or relationship, implied or otherwise, with this physician. The purpose of citing this doctor is to acknowledge, acknowledge and commend the exhaustive research and development work done by the scientists working on this peptide.
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