In summary, a final formulation has been designed including an active peptide targeting lipid droplet breakdown and macrophageclustering, encased in a liposome delivery system ensuring absorption through the hair follicle route, delivery to dWAT and ensuing signaling to sWAT compartments. Clinical tests comparing the formulation with a sham product following hot and cold non-invasive fat reduction procedures have been completed (in submission) and others are underway. Results thus far are extremely exciting and publications will follow.Unresolved issues particularly with cryolipolysis, include ‘Paradoxical adipose hyperplasia’ where unexpected overgrowth ofadipose tissue occurs in the area of treatment in a small number of patients.26,27 Pathogenesis is unknown and may well be related to droplet persistence or exosome stimulation of adipogenesis in these patients although no direct evidence exists for this at this time.
Non-surgical fat reduction remains an extremely popular procedure with varied technologies being used for this indication. When utilizing a technology that accesses a non-invasive closed route to the target tissue, it presents a challenge for removal of waste products created by the process. This paper presents some novel approaches for entry to the target region via topical applications and for subsequent breakdown and repackaging of lipid droplets through the autophagic/lipophagic mechanism. Thus, by designing liposome encased peptides, these may be preferentially delivered via hair follicles to dWAT, a newly recognized fat compartment that communicates directly with sWAT in humans. The peptides, primed to stimulate autophagic processes, result in further lipid droplet breakdown and macrophage clustering. This combination shows promise for facilitating and hastening recovery following non-surgical fat reduction procedures.
Alan D. Widgerow is Chief Medical Officer of Alastin Skincare Inc (Carlsbad CA). Products and funding for trials provided by company. Dr. Suzanne Kilmer is a consultant for Alastin Skincare, Inc. Dr. W. Grant Stevens is a consultant for Alastin Skincare, Inc.
1. Garibyan L, Sipprell WH, 3rd, Jalian HR, Sakamoto FH, Avram M, Anderson RR. Three-dimensional volumetric quantification of fat loss following cryolipolysis. Lasers Surg Med 2014;46(2):75-80.2. Duncan DI, Kim TH, Temaat R. A prospective study analyzing the application of radiofrequency energy and high-voltage, ultrashort pulse duration electrical fields on the quantitative reduction of adipose tissue. J Cosmet Laser Ther 2016;18(5):257-67.3. Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D, Anderson RR. Selective cryolysis: A novel method of non-invasive fat removal. Lasers Surg Med 2008;40(9):595-604.4. Pereira J, Cavalcante Y, Wanzeler R. The role of inflammation in adipocytolytic nonsurgical esthetic procedures for body contouring. Clin Cosmet Investig Dermatol 2017;10:57-66.5. Kilmer SL, Burns AJ, Zelickson BD. Safety and efficacy of cryolipolysis for non-invasive reduction of submental fat. Lasers Surg Med 2016;48(1): 3-13.6. Ingargiola MJ, Motakef S, Chung MT, Vasconez HC, Sasaki GH. Cryolipolysis for fat reduction and body contouring: safety and efficacy of current treatment paradigms. Plast Reconstr Surg 2015;135(6):1581-90.7. Bani D, Quattrini Li A, Freschi G, Russo GL. Histological and ultrastructural effects of ultrasound-induced cavitation on human skin adipose tissue. Plast Reconstr Surg Glob Open 2013;1(6):e41.8. Grant RW, Stephens JM. Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis. Am J Physiol Endocrinol Metab 2015;309(3):E205-13.9. Gregory CD, Devitt A. The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically? Immunology 2004;113(1):1-14.10. Maixner N, Kovsan J, Harman-Boehm I, Bluher M, Bashan N, Rudich A. Autophagy in adipose tissue. Obes Facts 2012;5(5):710-21.11. Wang CW. Lipid droplets, lipophagy, and beyond. Biochim Biophys Acta 2016;1861(8 Pt B):793-805.12. Singh R, Cuervo AM. Lipophagy: connecting autophagy and lipid metabolism. Int J Cell Biol 2012;2012:282041.13. Cappellano G, Ploner C. Dermal white adipose tissue renewal is regulated by the PDGFA/AKT axis. Stem Cell Investig 2017;4:23.14. Driskell RR, Jahoda CA, Chuong CM, Watt FM, Horsley V. Defining dermal adipose tissue. Exp Dermatol 2014;23(9):629-31.15. Chiang RS, Borovikova AA, King K, et al. Current concepts related to hypertrophic scarring in burn injuries. Wound Repair Regen 2016;24(3):466-77.16. Kruglikov I, Scherer PE. Skin aging: are adipocytes the next target? Aging 2016; 8(7):1457-68.17. Donati G, Proserpio V, Lichtenberger BM, et al. Epidermal Wnt/beta-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors. Proc Natl Acad Sci USA 2014;111(15):E1501-9.18. Plikus MV, Guerrero-Juarez CF, Ito M, et al. Regeneration of fat cells from myofibroblasts during wound healing. Science 2017;355(6326):748-52.19. Jain SK, Verma A, Jain A, Hurkat P. Transfollicular drug delivery: current perspectives. Research and Reports in Transdermal Drug Delivery 2016.20. Verma D. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm 2003;258(1-2):141-51.21. Vogt A, Combadiere B, Hadam S, et al. 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin. J Invest Dermatol 2006;126(6):1316-22.22. Cianfanelli V, De Zio D, Di Bartolomeo S, Nazio F, Strappazzon F, Cecconi F. Ambra1 at a glance. J Cell Sci 2015;128(11):2003-8.23. Marino G, Uria JA, Puente XS, Quesada V, Bordallo J, Lopez-Otin C. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J Biol Chem 2003;278(6):3671-8.24. Wu H, Che X, Zheng Q, et al. Caspases: a molecular switch node in the crosstalk between autophagy and apoptosis. Int J Biol Sci 2014;10(9):1072-83.25. Codogno P, Meijer A. Atg5: more than an autophagy factor. Nature Cell Biology 2006;8(10):1045-8.26. Jalian HR, Avram MM, Garibyan L, Mihm MC, Anderson RR. Paradoxical adipose hyperplasia after cryolipolysis. JAMA Dermatol 2014;150(3):317-9.27. Seaman SA, Tannan SC, Cao Y, Peirce SM, Gampper TJ. Paradoxical adipose hyperplasia and cellular effects after cryolipolysis: a case report. Aesthetic Surg J 2016;36(1):NP6-13.