The Role of Polyenylphosphatidylcholine (PPC) for the Reduction of Fat Pads in Deoxycholate Containing Injectables
Main Article Content
Abstract
Abstract
Increasing numbers of patients request lipolytic injection therapy for aesthetic indications instead of surgical procedures. Deoxycholic acid (DC) with or without phosphatidylcholine (PC) is widely used to reduce localized fat accumulation and lipomas. DC induces inflammation and reduces the adipocytes by necrosis, and the usefulness is controversially debated.
After the principal fat degrading process of injection adipolysis (IL) is described, and the special feature of PPC from soybean is characterized, the article summarizes its specific role for the transport of fat from peripheral tissue over blood to the liver, its influence on the activity of fat degrading enzymes, and on mitochondrial functions in the consent of IL. The interrelation between a strong inflammation by too quick adipocyte necrosis and mitochondrial dysfunction is considered to lead to decreased ß-fatty acid oxidation, while PPC improves mitochondrial structure and functioning. Besides a regulating influence of PPC on DC induced increased inflammation and its consequences on patient’s symptoms, apoptosis of PPC on adipocytes is discussed as additional mode of action in IL. Finally, PPC reduces DC’s side-effect profile and potential toxicity.
It is concluded that DC leads to fat cell necrosis, and PPC regulates this inflammatory process and adds apoptosis as second mode of action in fat tissue. Additionally, PPC reduces the side-effect and toxicity profile of DC.Article Details
How to Cite
GUNDERMANN, Karl-Josef et al.
The Role of Polyenylphosphatidylcholine (PPC) for the Reduction of Fat Pads in Deoxycholate Containing Injectables.
Medical Research Archives, [S.l.], v. 5, n. 8, aug. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1441>. Date accessed: 19 apr. 2024.
Keywords
Injection adipolysis, injection lipolysis, fat reduction, necrosis, apoptosis, phosphatidylcholine, deoxycholate, PC/DC
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1 Rittes PG. The use of phosphatidylcholine for correction of lower lid bulging due to prominent fat pads. Dermatol Surg 2001; 27(4): 391-392.
2 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(7): 1001-1008.
3 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(2): 419-427.
4 Chung SJ, Chung HL, Ho SL, Sung TK, Uy DS, Eon SP, Joon SB, Jong HL, Yoon HC, Ji HJ. The role of phosphatidylcholine and deoxycholic acid in inflammation. Life Sci 2014; 108(2):88-93.
5 Lieber CS, Robins SJ, Li J, DeCarli LM, Mak KM, Fasulo JM, Leo MA. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon, Gastroenterology 1994; 106(1): 152-159.
6 Desreumaux C, Dedonder E, Dewailly P, Sézille G, Fruchart JC. Effects of unsaturated fatty acids in phospholipids on the in vitro activation of the lipoprotein lipase and the triglyceride lipase. Drug Res 1979; 29(10): 1581-1583.
7 Rosseneu M, Declercq B, Vandamme D, Vercaemst R, Soetewey F, Peeters H, Blaton V. Influence of oral polyunsaturated and saturated phospholipid treatment on the lipid composition and fatty acid profile of chimpanzee lipoproteins. Atherosclerosis.1979; 32(2): 141-153.
8 Zierenberg O, Assmann G, Schmitz G, Rosseneu M. Effect of polyenylphosphatidylcholine on cholesterol uptake by human high density lipoprotein. Atherosclerosis 1981; 39(4): 527-542.
9 Spann W, Wolfram G, Zöllner N. Effects of equal amounts of linoleic acid in orally administered, polyunsaturated phospholipids or in safflower oil on blood lipoproteins. Klin Wochenschr 1987; 65(20): 980-984.
10 Spann W, Wolfram G, Zöllner N. Decrease of serum lipoproteins and increase inapolipoproteins A-I and A-II following oral administration of multiple unsaturated phospholipids. Observations on the effect of nutrition on the results. Klin Wochenschr 1987; 65(13): 590-595.
11 Jimenez MA, Scarino ML, Vignolini F, Mengheri E.Evidence that polyunsaturated lecithin induces a reduction in plasma cholesterol level and favorable changes in lipoprotein composition in hypercholesterolemic rats. J Nutr 1990; 120(7): 659-667.
12 Verghese PB, Arrese EL, Soulages JL. Stimulation of lipolysis enhances the rate of cholesterol efflux to HDL in adipocytes. Mol Cell Biochem 2007; 302(1-2): 241-248.
13 Kuntz E. „Essential“ phospholipids in hepatology - 50 years of experimental and clinical experience. Z Gastroenterol 1991; 29(suppl 2): 7-13.
14 Chatterjee C, Young EK, Pussegoda KA, Twomey EE, Pandey NR, Sparks DL. Hepatic high-density lipoprotein secretion regulates the mobilization of cell-surface hepatic lipase. Biochemistry 2009; 48(25): 5994-6001.
15 Oette K, Kühn G, Römer A, Niemann R, Gundermann K-J, Schumacher R. The absorption of dilinoleoylphosphatidylcholine after oral absorption. Drug Res 1995; 45(8): 875-879.
16 Gundermann KJ. The „essential“ phospholipids as a membrane therapeutic. European Society of Biomedical Pharmacology, JotA press Szczecin, Poland 1993.
17 Ellithorpe RA, Settineri R, Jacques B, Nicolson GL. Lipid replacement therapy functional food with NT factor for reducing weight, girth, body mass, appetite, carvings for foods and fatigue while improving blood lipid profiles. Funct Food Health Dis 2012;2(1): 11-24.
18 Nicolson GL, Ash ME: Lipid Replacement Therapy: a natural medicine approach to replacing damaged lipids in cellular membranes and organelle and restoring function. Biochim Biophys Acta2014; 1838(6): 1657-1679.
19 Galluzzi L, Kepp O, Trojel-Hansen C, Kroemer G. Mitochondrial control of cellular life, stress, and death. Circ Res 2012; 111(9): 1198-1207.
20 Navder KP, Lieber CS. Dilinoleoylphosphatidylcholine is responsible for the beneficial effects of polyenylphosphatidylcholine on ethanol-induced mitochondrial injury in rats. Biochem Biophys Res Commun 2002; 291(4): 1109-1112.
21 Duncan D, Rotunda AM. Injectable therapies for localized fat loss: state of the art. Clin Plast Surg 2011; 38(3): 489-501, vii.
22 Li H, Lee JH, Kim SY, Yun HY, Baek KJ, Kwon NS, Yoon Y, Jeong JH, Kim DS. Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes. J Biomed Sci 2011 Dec.7; 18: 91.
23 Sakakima Y, Hayakawa A, Nagasaka T, Nakao A. Prevention of
hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in
vivo experiments. J Hepatol 2007; 47(1): 83-92.
24 Sakakima Y, Hayakawa A, Nakao A. Phosphatidylcholine induces growth inhibition of hepatic cancer by apoptosis via death ligands. Hepato-Gastroenterol 2009; 56(90): 481-484.
25 Kim J-Y, Kwon M-S, Son J, Kang S-W. Selective effect of phosphatidylcholine on the lysis of adipocytes. PLoS ONE 2017; 12(5): e0176722.
26 Nagasaka Y, Inai S, Osumi Y, Takaori S, Shimamoto K. Acute and subacute toxicities of the essential phospholipids injection. Pharmacometrics 1969; 3(1): 45-56.
27 Hasengschwandtner F, Gundermann K-J. Injection lipolysis with phosphatidylcholine and deoxycholate.Aesthet Surg J 2013; 33(7): 1071-1072.
28 Duncan DI.Letter to the Editor – Response to “injection lipolysis with phosphatidylcholine and deoxycholate”.Aesthet Surg J 2013; 33(7): 1073-1075.
29 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(1): 60-66.
30 Duncan D, Rubin JP, Golitz L, Badylak S, Kesel L, Freund J, Duncan D. Refinement of technique in injection lipolysis based on scientific studies and clinical evaluation. ClinPlastSurg 2009; 36(2): 195-209.
31 Palumbo P, Melchiorre E, La Torre C, Miconi G, Cinque B, Marchesani G, Zoccali VG, Maione M, Macchiarelli G, Vitale AR, Leocata P, Cifone MG, Giuliani M. Effects of phosphatidylcholine and sodium deoxycholate on human primary adipocytes and fresh human adipose tissue. Int J Immunopathol Pharmacol 2010; 23(2): 481-489.
32 El-Hariri LM, Marriott C, Martin GP. The mitigating effects of phosphatidylcholines on bile salt- and lysophosphatidylcholine - induced membrane damage.J Pharm Pharmacol 1992; 44(8): 651-654.
33 Okazaki M, Hara I, Kobayashi T, Hayashi M. Effect of phosphatidylcholine on the hemolytic activities of bile salts. J Jap Oil Chem Soc 1980; 29(10): 743-747.
34 Martin GP, Marriott C. Membrane damage by bile salts: the protective function of phospholipids. J Pharm Pharmacol 1981; 33(12): 754-759.
35 Dial EJ, Dawson PA, Lichtenberger LM. In vitro evidence that phosphatidylcholine protects against indomethacin/bile acid-induced injury to cells. Am J Physiol Gastrointest Liver Physiol 2015; 308(3): G217-G222.
36 Dial EJ, Darling RL, Lichtenberger LM. Importance of biliary excretion of indomethacin in gastrointestinal and hepatic injury. J Gastroenterol Hepatol 2008; 23(8 Pt2): e384-e389.
37 Dial EJ, Rooijakkers SHM, Darling RL, Romero JJ, Lichtenberger LM. Role of phosphatidylcholine saturation in preventing bile salt toxicity to gastrointestinal epithelia and membranes. J Gastroenterol Hepatol 2008; 23(3): 430-436.
38 Dial EJ, Doyen JR, Lichtenberger LM. Phosphatidylcholine-associated nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit DNA synthesis and the growth of colon cancer cells in vitro. Cancer Chemother Pharmacol 2006; 57(3): 295-300.
39 Tan Y, Qi J, Lu Y, Hu F, Yin Z, Wu W. Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells. Toxicol In Vitro 2013; 27(2): 714-720.
40 Ikeda Y, Morita S-y, Terada T. Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts. Sci Rep 2017; 7(1): 306.
41Weidmann M, Lettko M, Prantl L. Injektionslipolyse. J Ästhet Chir DOI 10.1007/s12631-016-0047-2.
42 http://reference.medscape.com/drug/kybella-deoxycholic-acid-999993
43 Kamalpour S, Leblanc Jr K. Injection adipolysis: mechanisms, agents, and future directions. JCAD 2016; 9(12): 44-50.
44 Humphrey S, Sykes J, Kantor J, Bertucci V, Walker P, Lee DR, Lizzul PF, Gross TM, Beddingfield FC 3rd. ATX-101 for reduction ofsubmental fat: a phase III randomized controlled trial. J Am Acad Dermatol 2016; 75(4): 788-797.e7.
45 Tausch I, Kruglikov I. The benefit of dual-frequency ultrasound in patients treated by injection lipolysis.J Clin Aesthet Dermatol 2015; 8(8): 42-46.
46 Sandhofer M, Schauer P, Faulhaber J. Untersuchungsergebnisse des nicht-operativen Bodycontouring mittels Kombination aus Kryolipolyse, IL und Stoßwelle an 22 Patienten. Spitzenforschung Ästhet.Dermatol.Dermatochir., Annual Magazine 2017, pp.122-125
47 Gundermann K-J, Kuenker A, Kuntz E, Droździk M. Activity of essential phospholipids (EPL) from soybean in liver diseases. Pharmacol Rep 2011; 63(3): 643-659.
48 Gundermann K-J, Gundermann S, Drozdzik M, Prasad M. Essential phospholipids in fatty liver: a scientific update. Clin Exp Gastroenterol 2016; 9(May 05): 105-117.
2 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(7): 1001-1008.
3 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(2): 419-427.
4 Chung SJ, Chung HL, Ho SL, Sung TK, Uy DS, Eon SP, Joon SB, Jong HL, Yoon HC, Ji HJ. The role of phosphatidylcholine and deoxycholic acid in inflammation. Life Sci 2014; 108(2):88-93.
5 Lieber CS, Robins SJ, Li J, DeCarli LM, Mak KM, Fasulo JM, Leo MA. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon, Gastroenterology 1994; 106(1): 152-159.
6 Desreumaux C, Dedonder E, Dewailly P, Sézille G, Fruchart JC. Effects of unsaturated fatty acids in phospholipids on the in vitro activation of the lipoprotein lipase and the triglyceride lipase. Drug Res 1979; 29(10): 1581-1583.
7 Rosseneu M, Declercq B, Vandamme D, Vercaemst R, Soetewey F, Peeters H, Blaton V. Influence of oral polyunsaturated and saturated phospholipid treatment on the lipid composition and fatty acid profile of chimpanzee lipoproteins. Atherosclerosis.1979; 32(2): 141-153.
8 Zierenberg O, Assmann G, Schmitz G, Rosseneu M. Effect of polyenylphosphatidylcholine on cholesterol uptake by human high density lipoprotein. Atherosclerosis 1981; 39(4): 527-542.
9 Spann W, Wolfram G, Zöllner N. Effects of equal amounts of linoleic acid in orally administered, polyunsaturated phospholipids or in safflower oil on blood lipoproteins. Klin Wochenschr 1987; 65(20): 980-984.
10 Spann W, Wolfram G, Zöllner N. Decrease of serum lipoproteins and increase inapolipoproteins A-I and A-II following oral administration of multiple unsaturated phospholipids. Observations on the effect of nutrition on the results. Klin Wochenschr 1987; 65(13): 590-595.
11 Jimenez MA, Scarino ML, Vignolini F, Mengheri E.Evidence that polyunsaturated lecithin induces a reduction in plasma cholesterol level and favorable changes in lipoprotein composition in hypercholesterolemic rats. J Nutr 1990; 120(7): 659-667.
12 Verghese PB, Arrese EL, Soulages JL. Stimulation of lipolysis enhances the rate of cholesterol efflux to HDL in adipocytes. Mol Cell Biochem 2007; 302(1-2): 241-248.
13 Kuntz E. „Essential“ phospholipids in hepatology - 50 years of experimental and clinical experience. Z Gastroenterol 1991; 29(suppl 2): 7-13.
14 Chatterjee C, Young EK, Pussegoda KA, Twomey EE, Pandey NR, Sparks DL. Hepatic high-density lipoprotein secretion regulates the mobilization of cell-surface hepatic lipase. Biochemistry 2009; 48(25): 5994-6001.
15 Oette K, Kühn G, Römer A, Niemann R, Gundermann K-J, Schumacher R. The absorption of dilinoleoylphosphatidylcholine after oral absorption. Drug Res 1995; 45(8): 875-879.
16 Gundermann KJ. The „essential“ phospholipids as a membrane therapeutic. European Society of Biomedical Pharmacology, JotA press Szczecin, Poland 1993.
17 Ellithorpe RA, Settineri R, Jacques B, Nicolson GL. Lipid replacement therapy functional food with NT factor for reducing weight, girth, body mass, appetite, carvings for foods and fatigue while improving blood lipid profiles. Funct Food Health Dis 2012;2(1): 11-24.
18 Nicolson GL, Ash ME: Lipid Replacement Therapy: a natural medicine approach to replacing damaged lipids in cellular membranes and organelle and restoring function. Biochim Biophys Acta2014; 1838(6): 1657-1679.
19 Galluzzi L, Kepp O, Trojel-Hansen C, Kroemer G. Mitochondrial control of cellular life, stress, and death. Circ Res 2012; 111(9): 1198-1207.
20 Navder KP, Lieber CS. Dilinoleoylphosphatidylcholine is responsible for the beneficial effects of polyenylphosphatidylcholine on ethanol-induced mitochondrial injury in rats. Biochem Biophys Res Commun 2002; 291(4): 1109-1112.
21 Duncan D, Rotunda AM. Injectable therapies for localized fat loss: state of the art. Clin Plast Surg 2011; 38(3): 489-501, vii.
22 Li H, Lee JH, Kim SY, Yun HY, Baek KJ, Kwon NS, Yoon Y, Jeong JH, Kim DS. Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes. J Biomed Sci 2011 Dec.7; 18: 91.
23 Sakakima Y, Hayakawa A, Nagasaka T, Nakao A. Prevention of
hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in
vivo experiments. J Hepatol 2007; 47(1): 83-92.
24 Sakakima Y, Hayakawa A, Nakao A. Phosphatidylcholine induces growth inhibition of hepatic cancer by apoptosis via death ligands. Hepato-Gastroenterol 2009; 56(90): 481-484.
25 Kim J-Y, Kwon M-S, Son J, Kang S-W. Selective effect of phosphatidylcholine on the lysis of adipocytes. PLoS ONE 2017; 12(5): e0176722.
26 Nagasaka Y, Inai S, Osumi Y, Takaori S, Shimamoto K. Acute and subacute toxicities of the essential phospholipids injection. Pharmacometrics 1969; 3(1): 45-56.
27 Hasengschwandtner F, Gundermann K-J. Injection lipolysis with phosphatidylcholine and deoxycholate.Aesthet Surg J 2013; 33(7): 1071-1072.
28 Duncan DI.Letter to the Editor – Response to “injection lipolysis with phosphatidylcholine and deoxycholate”.Aesthet Surg J 2013; 33(7): 1073-1075.
29 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(1): 60-66.
30 Duncan D, Rubin JP, Golitz L, Badylak S, Kesel L, Freund J, Duncan D. Refinement of technique in injection lipolysis based on scientific studies and clinical evaluation. ClinPlastSurg 2009; 36(2): 195-209.
31 Palumbo P, Melchiorre E, La Torre C, Miconi G, Cinque B, Marchesani G, Zoccali VG, Maione M, Macchiarelli G, Vitale AR, Leocata P, Cifone MG, Giuliani M. Effects of phosphatidylcholine and sodium deoxycholate on human primary adipocytes and fresh human adipose tissue. Int J Immunopathol Pharmacol 2010; 23(2): 481-489.
32 El-Hariri LM, Marriott C, Martin GP. The mitigating effects of phosphatidylcholines on bile salt- and lysophosphatidylcholine - induced membrane damage.J Pharm Pharmacol 1992; 44(8): 651-654.
33 Okazaki M, Hara I, Kobayashi T, Hayashi M. Effect of phosphatidylcholine on the hemolytic activities of bile salts. J Jap Oil Chem Soc 1980; 29(10): 743-747.
34 Martin GP, Marriott C. Membrane damage by bile salts: the protective function of phospholipids. J Pharm Pharmacol 1981; 33(12): 754-759.
35 Dial EJ, Dawson PA, Lichtenberger LM. In vitro evidence that phosphatidylcholine protects against indomethacin/bile acid-induced injury to cells. Am J Physiol Gastrointest Liver Physiol 2015; 308(3): G217-G222.
36 Dial EJ, Darling RL, Lichtenberger LM. Importance of biliary excretion of indomethacin in gastrointestinal and hepatic injury. J Gastroenterol Hepatol 2008; 23(8 Pt2): e384-e389.
37 Dial EJ, Rooijakkers SHM, Darling RL, Romero JJ, Lichtenberger LM. Role of phosphatidylcholine saturation in preventing bile salt toxicity to gastrointestinal epithelia and membranes. J Gastroenterol Hepatol 2008; 23(3): 430-436.
38 Dial EJ, Doyen JR, Lichtenberger LM. Phosphatidylcholine-associated nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit DNA synthesis and the growth of colon cancer cells in vitro. Cancer Chemother Pharmacol 2006; 57(3): 295-300.
39 Tan Y, Qi J, Lu Y, Hu F, Yin Z, Wu W. Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells. Toxicol In Vitro 2013; 27(2): 714-720.
40 Ikeda Y, Morita S-y, Terada T. Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts. Sci Rep 2017; 7(1): 306.
41Weidmann M, Lettko M, Prantl L. Injektionslipolyse. J Ästhet Chir DOI 10.1007/s12631-016-0047-2.
42 http://reference.medscape.com/drug/kybella-deoxycholic-acid-999993
43 Kamalpour S, Leblanc Jr K. Injection adipolysis: mechanisms, agents, and future directions. JCAD 2016; 9(12): 44-50.
44 Humphrey S, Sykes J, Kantor J, Bertucci V, Walker P, Lee DR, Lizzul PF, Gross TM, Beddingfield FC 3rd. ATX-101 for reduction ofsubmental fat: a phase III randomized controlled trial. J Am Acad Dermatol 2016; 75(4): 788-797.e7.
45 Tausch I, Kruglikov I. The benefit of dual-frequency ultrasound in patients treated by injection lipolysis.J Clin Aesthet Dermatol 2015; 8(8): 42-46.
46 Sandhofer M, Schauer P, Faulhaber J. Untersuchungsergebnisse des nicht-operativen Bodycontouring mittels Kombination aus Kryolipolyse, IL und Stoßwelle an 22 Patienten. Spitzenforschung Ästhet.Dermatol.Dermatochir., Annual Magazine 2017, pp.122-125
47 Gundermann K-J, Kuenker A, Kuntz E, Droździk M. Activity of essential phospholipids (EPL) from soybean in liver diseases. Pharmacol Rep 2011; 63(3): 643-659.
48 Gundermann K-J, Gundermann S, Drozdzik M, Prasad M. Essential phospholipids in fatty liver: a scientific update. Clin Exp Gastroenterol 2016; 9(May 05): 105-117.