Injection Adipolysis: Mechanisms, Agents, and Future Directions
- ️https://independent.academia.edu/ShahraamKamalpour
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Archives of Plastic Surgery, 2012
Background Phosphatidylcholine (PPC) and deoxycholate (DCA) compound has been recently used for the purpose of partial lipolysis and is valued for its efficacy and lower invasiveness compared to liposuction and dermolipectomy used previously. In this article, the authors discuss the efficacy of the PPC dissolved in DCA via an experimental rat study model, along with suggesting a useful animal experimental model for the study of adipose tissue and lipolysis. Methods Bilateral inguinal fat pads of an experimental rat were elevated with the deep inferior epigastric vessel as the sole vascular pedicle. Normal saline was injected on one side as a control group and a PPC and DCA compound was injected on the other side. After 4 days, the rats were euthanized for microscopic tissue examination. The pathology was scored by a semiquantitative system in 4 categories: normal fat amount, fat necrosis, inflammatory activity, and stage of fibrosis. A Wilcoxon signed-rank test powered by SPSS packe...
Plastic and Reconstructive Surgery - Global Open, 2018
Background: The use of deoxycholic acid to reduce localized fat deposits is a procedure that has been in use for about 30 years. Its effectiveness as treatment is due to emulsification of phospholipids and therefore, solubilization of the biological membranes with resulting fat necrosis. The purpose of the study was to assess the effectiveness and the safety of an injectable solution containing sodium deoxycholtate 1.25% (DB125), used as intralipotherapy. Methods: The effectiveness and safety of DB125 solution have been assessed with a multicentre observational prospective study carried out between February and October 2017. The 221 selected patients presented with various forms and degrees of localized fat in several areas. Intralipotherapy treatments were performed 6 weeks apart and until the clinical result was obtained. Aesthetic outcomes were evaluated by the authors using preoperative and postoperative photographic documentation and by the patients with their level of satisfaction by filling out an anonymous form. Major adverse events were reported by each doctor who performed the treatment. Results: Two hundred twenty-one patients treated in 273 cases of different localized fat deposits. One hundred eighty-five patients who could be assessed for final results gave the effectiveness of the treatment an average score of 7.4. The failure percentage of the treatment was 3.8%. The medical evaluation showed treatment success in 93.5% of cases. Adverse events can be divided into 2 groups: minor adverse events, which are very frequent and major ones, which are extremely rare. For both groups, the adverse events can be ascribed to localized problems in the treatment area. Conclusion: Studies have shown that the second-generation solution containing sodium deoxycholate 1.25% is effective and safe to treat different localized fat deposits. The high degree of effectiveness shown in the study was not associated with a lesser degree of handling because, at the doses indicated and with the use of intralipotherapy, the occurrence of adverse events was minimal.
A Pilot Study on the Use of Injection Lipolysis in Visceral Adipose Tissues
Aesthetic Surgery Journal, 2013
Background: Intraperitoneal fat, also known as visceral adipose tissue (VAT), poses significant metabolic risks. Reduction of this fat is functionally and aesthetically desirable. Since surgical reduction has serious risks, a noninvasive method for reduction of this fat would have important clinical benefits. Objective: The authors evaluate the reduction in VAT in an animal model using injection lipolysis. Methods: Phosphatidylcholine was injected in half of the omentum of 16 dogs (weight 30-40 kg) by surgical laparotomy. The dogs' vital signs were followed postoperatively. A second laparotomy was performed at 2 weeks (n = 10), 4 weeks (n = 4), or 6 weeks (n = 2). Reduction of fat in the injected side was assessed by comparing with the control side. Specimens of the injected and the control sides were examined microscopically. Intraperitoneal cultures were also obtained. Results: There was a major reduction in the amount of fat in all 16 dogs. No intraperitoneal abscesses, collections, or adhesions developed, and there was no injury to any intra-abdominal organs. Microscopic examination showed significant fat loss and lysis of fat cells with cellular infiltrate formed of predominantly macrophages, with fibrosis developing in the 6-week specimens. No bacterial or fungal growth was observed on the cultures. The dogs' vital signs showed no significant variation from the preoperative baseline. Conclusions: Injection lipolysis is effective and safe in reducing VAT in dogs. Further studies are needed to prove its efficacy and safety in humans and refine its indications and method of injection.
International Journal of Immunopathology and Pharmacology, 2010
Recent studies introduced the novel concept of chemical lipolysis where phosphatidylcholine (PC), an active component of commercial preparations, plays a pivotal role. Other studies suggested that sodium deoxycholate (DOC), an excipient contained in medical preparations, could be the real active component performing an adipocytolytic action. We investigated the effects of PC and DOC on human primary adipocyte cultures and on human fresh adipose tissue. Human adipocytes isolated by Rodbell's method, were cultured onto type I collagen-coated glass coverslips, placed into 24-well tissue culture plates. Cells were incubated with or without DOC (5–7–9%), PC (5%) or DOC/PC mixture and observed under phase contrast microscope. After incubation, cells were stained with Oil Red-O and with acridine orange/ethidium bromide to observe necrotic cells with phase contrast microscope and fluorescent microscope, respectively. Histological specimens from adipose tissue biopsies were observed with...
Tissue-Selective Effects of Injected Deoxycholate
Dermatologic Surgery, 2010
BACKGROUND Recent studies suggest that the principal active ingredient in phosphatidylcholinecontaining injectable fat-reduction formulations is actually deoxycholate (DC). This bile acid acts as a detergent to rapidly disrupt cell membranes. Thus, it is not obvious why DC would preferentially target fat. OBJECTIVE To investigate possible mechanisms for the selectivity of DC for fat tissue using in vivo and in vitro models. METHODS AND MATERIALS Histology, drug distribution studies, and cell viability assays were used to examine possible mechanisms contributing to DC selectivity. In vitro, DC caused the lysis of all cell types tested within the tested concentration range. DC injected into fat tissue caused adipocyte death, whereas other cell types appeared less affected. Physiological concentrations of albumin or protein-rich tissues decrease the ability of DC to lyse cells. Furthermore, DC relocated to the gastrointestinal tract in animals within hours of injection. This suggests that similar mechanisms may be present in humans. CONCLUSION We report observations that provide a possible explanation for the in vivo preferential fat targeting by DC. Fat tissue, being deficient in cell-associated proteins and interstitial albumin, may be unable to sufficiently neutralize the detergent activity of DC, possibly making fat uniquely sensitive to DC. This study was funded by a grant from Kythera. Drs. Bentow and Knopp are consultants for Kythera, and Nadir Mahmood and Nathaniel David are employees of Kythera.
Safe and effective subcutaneous adipolysis in minipigs by a collagenase derivative
PLOS ONE, 2019
Adipocytes attached to the extracellular matrix (ECM) mainly consist of collagen in adipose tissues, while the degradation of ECM by collagenase induces the apoptosis of adipocytes, leading to a decrease in local subcutaneous adipose. To achieve this goal, we are developing a mutant collagenase H (ColH) to remove local subcutaneous fat such as submental fat (SMF). Three vectors were constructed for expressing rColH(FM, mutant for fat melting, with 6xHis tag), rColH(WT, wild-type, with 6xHis tag), and rColH(E451D, E451D mutant, without 6xHis tag) in Escherichia coli. rColH(FM) & rColH(WT) were purified by Ni Sepharose on a laboratory scale, while rColH(E451D) was purified by five chromatography purification steps on a large scale. Then, the stability of rColH(FM) and rColH(WT) was tested by SDS-PAGE to investigate the influence of the E451D mutation on stability. Afterwards, the enzyme kinetics of ColH (mutant or wild-type, with or without His tag) were investigated and compared. Finally, the adipolysis of rColH(E451D) at various doses was tested in vitro and in vivo. The ultrasound results in minipigs suggested that effective adipolysis was induced by rColH(E451D) compared with the negative control, and the histological results suggest dose-dependent fibrosis, necrosis, inflammation and cholesterol cleft formation. These findings indicate the possibility of rColH(E451D) becoming a new injectable drug to safely remove subcutaneous adipose.
Lipomas treated with subcutaneous deoxycholate injections
Journal of the American Academy of Dermatology, 2005
Background: Lipomas are benign neoplasms of mature fat cells. Current treatments are invasive and carry the risk of scarring. Injections of phosphatidylcholine solubilized with deoxycholate, a bile salt, have been used to reduce unwanted accumulations of fat. Recent in vitro and ex vivo investigations indicate that deoxycholate alone causes adipocyte lysis. Objective: We sought to report our experience treating lipomas using subcutaneous deoxycholate injections. Methods: A total of 6 patients presenting with 12 lipomas were treated with intralesional injections of sodium deoxycholate (1.0%, 2.5%, and 5.0%) at intervals of 2 to 20 weeks. Tumor size, cutaneous reactions, and patients' subjective responses were recorded before and after treatment. Results: All lipomas decreased in size (mean area reduction, 75%; range, 37%-100%) as determined by clinical measurement (with ultrasound confirmation in one lipoma) after an average of 2.2 treatments. Several lipomas fragmented or became softer in addition to decreasing in volume. Adverse effects, including transient burning, erythema, and local swelling, were associated with higher deoxycholate concentrations but resolved without intervention. There was no clear association between deoxycholate concentration and efficacy. Conclusions: Our clinical experience supports our laboratory investigations demonstrating that deoxycholate, rather than phosphatidylcholine, is the active ingredient in subcutaneously injected formulas used to treat adipose tissue. This small series suggests that low concentration deoxycholate may be a relatively safe and effective treatment for small collections of fat. However, controlled clinical trials will be necessary to substantiate these observations. (
Journal of Cosmetic Dermatology, 2020
BackgroundDeoxycholic acid (DCA) was developed by the pharmaceutical industry for aesthetical use in submental fat reduction. It represents the first lipolytic substance approved by the Food and Drug Administration (FDA) for fat reduction in that area.AimsThis study presents an update of properties and the use of DCA, as well as adverse events and possible complications.MethodsA search in MEDLINE/PubMed, Cochrane, and Bireme/LILACS databases was performed using the terms: “deoxycholic acid” OR “ATX‐101” AND “injection” NOT “amphotericin” NOT “biliary” NOT “bile.” Experimental studies developed in animals, clinical trials, literature reviews, case reports, and letters to the editor that included the DCA mechanism of action, dose, manner of use, adverse effects, and complications were selected.ResultsThe most frequent adverse events are edema, local pain, bruise, and numbness, which usually spontaneously regress. However, complications, including, skin necrosis, nerve injury, alopecia...