Tissue‐Selective Effects of Injected Deoxycholate

• Published in: Dermatologic surgery 2010-06, Vol.36 (6), p.899-908
• Main Authors: THUANGTONG, RATTAPON, BENTOW, JASON J., KNOPP, KRISTEENE, MAHMOOD, NADIR A., DAVID, NATHANIEL E., KOLODNEY, MICHAEL S.
• Format: Article
• Language: English
• Subjects: Adipocytes - drug effects; Animals; Biological and medical sciences; Cell Culture Techniques; Cholagogues and Choleretics - administration & dosage; Cholagogues and Choleretics - pharmacology; Deoxycholic Acid - administration & dosage; Deoxycholic Acid - pharmacology; Dermatology; Fibroblasts - drug effects; Humans; Injections, Subcutaneous; Keratinocytes - drug effects; Medical sciences; Mice; Mice, Obese; Models, Animal; Muscle Cells - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Skin - drug effects; Skin - metabolism; Skin - pathology; Skin plastic surgery; Subcutaneous Fat - drug effects; Subcutaneous Fat - metabolism; Subcutaneous Fat - pathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
• ISSN: 1076-0512; 1524-4725
• DOI: 10.1111/j.1524-4725.2010.01566.x

BACKGROUND Recent studies suggest that the principal active ingredient in phosphatidylcholine‐containing 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. RESULTS  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.