Detergent Effects of Sodium Deoxycholate Are a Major Feature of an Injectable Phosphatidylcholine Formulation Used for Localized Fat Dissolution

Rotunda, Adam M.; Suzuki, Hiroyuki; Moy, Ronald L.; Kolodney, Michael S.

doi:10.1111/j.1524-4725.2004.30305.x

Cited by 136 publications

(141 citation statements)

References 27 publications

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“…Suggested mechanisms have included emulsification, lysis of the cell membrane through detergent effects, and lipase activation that accelerates lipolysis. PPC is recognized as the active component of such formulations due to its emulsifying properties and lipid-lowering effects in serum upon intravenous injection or oral administration [20]. However, the mechanisms of action of PPC in adipocytes have not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylcholine Causes Lipolysis and Apoptosis in Adipocytes through the Tumor Necrosis Factor Alpha-Dependent Pathway

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

Phosphatidylcholine Causes Lipolysis and Apoptosis in Adipocytes through the Tumor Necrosis Factor Alpha-Dependent Pathway

et al. 2017

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“…Studies have shown the endogenous molecule deoxycholic acid to be the active lytic agent in previous injectable formulations [17–19]. As a proprietary, synthetically derived, purified formulation of deoxycholic acid, ATX-101 causes localized adipocytolysis when injected into subcutaneous fat.…”

Section: Introductionmentioning

confidence: 99%

Results from a Pooled Analysis of Two European, Randomized, Placebo-Controlled, Phase 3 Studies of ATX-101 for the Pharmacologic Reduction of Excess Submental Fat

McDiarmid¹,

Ruiz²,

Lee

et al. 2014

Aesth Plast Surg

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BackgroundThe injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies.MethodsPatients with unwanted SMF were randomized to receive 1 or 2 mg/cm2 of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded.ResultsSignificantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 28.6 % of the placebo recipients; p < 0.001 for both ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, vs. 34.3 % of the placebo recipients; p < 0.001 for both), analyzed alone or in combination, with ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, vs. 29.0 % of the placebo recipients; p < 0.001 for both). In this study, ATX-101 was effective irrespective of gender, age, or body mass index. Reduction in SMF with ATX-101 was confirmed by calliper measurements (p < 0.001 for both doses vs. placebo) and generally did not lead to worsening of skin laxity (SLRS improved or was unchanged: 91.3 and 90.5 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 91.6 % of the placebo recipients). Adverse events were mostly transient, mild to moderate in intensity, and localized to the treatment area.ConclusionThe findings show ATX-101 to be an effective and well-tolerated pharmacologic treatment for SMF reduction.Level of Evidence IThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

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“…[1] PC is viscous and, therefore, to facilitate its injection, an emulsifying agent, deoxycholate, is added, which is shown to independently cause lysis of the adipocytes. [9] (b) Promotes lipolysis by stimulating  receptors and inhibiting 2 receptors present on the adipocyte membrane, [10] (c) Also causes inflammatory cytokine-mediated necrosis and resorption of adipocytes. Once the inflammation subsides, new collagen is formed, leading to retraction of the loosened tissue.…”

Section: Cellulitementioning

confidence: 99%

Mesotherapy: What is new?

Konda¹,

Thappa²

2013

Indian J Dermatol Venereol Leprol

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Detergent Effects of Sodium Deoxycholate Are a Major Feature of an Injectable Phosphatidylcholine Formulation Used for Localized Fat Dissolution

Cited by 136 publications

References 27 publications

Phosphatidylcholine Causes Lipolysis and Apoptosis in Adipocytes through the Tumor Necrosis Factor Alpha-Dependent Pathway

Phosphatidylcholine Causes Lipolysis and Apoptosis in Adipocytes through the Tumor Necrosis Factor Alpha-Dependent Pathway

Results from a Pooled Analysis of Two European, Randomized, Placebo-Controlled, Phase 3 Studies of ATX-101 for the Pharmacologic Reduction of Excess Submental Fat

Mesotherapy: What is new?

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