A phosphatidylcholine (PPC) formulation has been used to treat cellulite; however, its underlying mechanism of action remains unclear. In this study, we demonstrated that PPC induces lipolysis and apoptosis in adipocytes, and evaluated a possible tumor necrosis factor alpha (TNFα)-dependent pathway, whereby PPC exerts these effects. For in vitro study, fully differentiated 3T3-L1 cells, mouse adipocytes were treated with various concentrations of PPC and cell apoptosis and lipolysis were assayed. For in vivo experiments, mice fed on a high-fat diet for 8 weeks were injected twice to abdominal subcutaneous fat tissues of either vehicle or PPC. We found that PPC induced lipolysis and apoptosis dose-dependently in fully differentiated 3T3-L1 cells. In addition, PPC augmented both expression and release of TNFα in a dose-dependent fashion. Induction of TNFα by PPC was associated with the stimulation of nuclear factor kappa B (NFκB)-mediated transcriptional activity. Small interfering RNA (siRNA)-mediated suppression of NFκB abrogated the effect of PPC on TNFα secretion. Suppression of TNFα with specific siRNA abrogated the effects of PPC on lipolysis and apoptosis. Through in vivo experiments, we demonstrated that PPC injection not only stimulated the local lipolysis and apoptosis, resulting in weight loss, but also induced TNFα mRNA expression and neutrophil infiltration. Furthermore, PPC injection prevented lipogenesis and suppressed the mRNA -expression of adipokines (such as adiponectin and leptin), due to the down-sizing of adipocytes. In conclusion, we suggest that PPC induces lipolysis and apoptosis in adipocytes through TNFα-dependent pathways.

Pistor M: What is mesotherapy?. Chir Dent Fr 1976; 46: 59–60.
Young VL: Lipostabil: the effect of phosphatidylcholine on subcutaneous fat. Aesthet Surg J 2003; 23: 413–417.
Ablon G, Rotunda AM: Treatment of lower eyelid fat pads using phosphatidylcholine: clinical trial and review. Dermatol Surg 2004; 30: 422–427; discussion 428.
Salti G, Ghersetich I, Tantussi F, Bovani B, Lotti T: Phosphatidylcholine and sodium deoxycholate in the treatment of localized fat: a double-blind, randomized study. Dermatol Surg 2008; 34: 60–66; discussion 66.
Gupta A, Lobocki C, Singh S, Robertson M, Akadiri OA, Malhotra G, Jackson IT: Actions and comparative efficacy of phosphatidylcholine formulation and isolated sodium deoxycholate for different cell types. Aesthetic Plast Surg 2009; 33: 346–352.
Duncan DI, Palmer M: Fat reduction using phosphatidylcholine/sodium deoxycholate injections: standard of practice. Aesthetic Plast Surg 2008; 32: 858–872.
Rotunda AM, Kolodney MS: Mesotherapy and phosphatidylcholine injections: historical clarification and review. Dermatol Surg 2006; 32: 465–480.
Rittes PG: The use of phosphatidylcholine for correction of localized fat deposits. Aesthetic Plast Surg 2003; 27: 315–318.
Rotunda AM, Ablon G, Kolodney MS: Lipomas treated with subcutaneous deoxycholate injections. J Am Acad Dermatol 2005; 53: 973–978.
Bechara FG, Sand M, Hoffmann K, Sand D, Altmeyer P, Stucker M: Fat tissue after lipolysis of lipomas: a histopathological and immunohistochemical study. J Cutan Pathol 2007; 34: 552–557.
Porter MH, Cutchins A, Fine JB, Bai Y, -DiGirolamo M: Effects of TNF-alpha on -glucose metabolism and lipolysis in -adipose tissue and isolated fat-cell -preparations. J Lab Clin Med 2002; 139: 140–146.
Hauner H, Petruschke T, Russ M, Rohrig K, Eckel J: Effects of tumour necrosis factor alpha (TNF alpha) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologia 1995; 38: 764–771.
Popa C, Netea MG, van Riel PL, van der Meer JW, Stalenhoef AF: The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 2007; 48: 751–762.
Prins JB, Niesler CU, Winterford CM, Bright NA, Siddle K, O’Rahilly S, Walker NI, Cameron DP: Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes 1997; 46: 1939–1944.
Porras A, Alvarez AM, Valladares A, Benito M: TNF-alpha induces apoptosis in rat fetal brown adipocytes in primary culture. FEBS Lett 1997; 416: 324–328.
Qian H, Hausman DB, Compton MM, Martin RJ, Della-Fera MA, Hartzell DL, Baile CA: TNFalpha induces and insulin inhibits caspase 3-dependent adipocyte apoptosis. Biochem Biophys Res Commun 2001; 284: 1176–1183.
Zhao X, Qi R, Sun C, Xie Y: Silencing SOCS3 could inhibit TNF-α induced apoptosis in 3T3-L1 and mouse preadipocytes. Mol Biol Rep 2012; 39: 8853–8860.
Steeg PS, Theodorescu D: Metastasis: a therapeutic target for cancer. Nat Clin Pract Oncol 2008; 5: 206–219.
Wang HQ, Liu BQ, Gao YY, Meng X, Guan Y, Zhang HY, Du ZX: Inhibition of the JNK signalling pathway enhances proteasome inhibitor-induced apoptosis of kidney cancer cells by suppression of BAG3 expression. Br J Pharmacol 2009; 158: 1405–1412.
Rotunda AM, Suzuki H, Moy RL, Kolodney MS: Detergent effects of sodium deoxycholate are a major feature of an injectable phosphatidylcholine formulation used for localized fat dissolution. Dermatol Surg 2004; 30: 1001–1008.
Porter AG, Janicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999; 6: 99–104.
Klein SM, Schreml S, Nerlich M, Prantl L: In vitro studies investigating the effect of subcutaneous phosphatidylcholine injections in the 3T3-L1 adipocyte model: lipolysis or lipid dissolution? Plast Reconstr Surg 2009; 124: 419–427.
Zhang HH, Halbleib M, Ahmad F, Manganiello VC, Greenberg AS: Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 2002; 51: 2929–2935.
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