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Prostaglandin F2a Analog Focally Depletes Adipose Volume Without Concurrent Cytolysis
Anya Singh-Varma, BS, Shawn Jeffrey Loder, MD, Joseph Sukinik, BS, Phoebe Lee, BS, Sarah Seman, BS, Wayne Vincent Nerone, BS, Solomon Su, PhD, Lauren Kokai, PhD.
University of Pittsburgh, Pittsburgh, PA, USA.

PURPOSE: Adipose is one of the most mutable and commonly treated tissues in plastic surgery. Adipose tissue is often the thickest and most variable of the cutaneous layers and is a key contributor to smooth contour, feature, and expression. Unwanted focal adiposity is a common complaint and can arise physiologically, pathologically as lipomas, or iatrogenically after fat grafting. While some indications are amenable to liposuction or resection, not all patients want invasive procedures. Non-invasive ablative procedures have arisen to fill this need including cryolipolysis and the injectable cytolytic deoxycholic acid (Kybella). This agent, however, caries significant comorbid risk. In this study, we investigated repurposing a potent FDA approved prostaglandin F2α (PGF2a) analogue, Latanoprost, currently used as first-line treatment for glaucoma, as an alternative adipolytic agent for small volume focal adipose reduction.
METHODS: Human adipose obtained under IRB exemption was incubated for 14-days and treated with Kybella and either low- or high-dose soluble Latanoprost every 48-hours. Mature adipocytes and the stromal vascular fractions were collected via enzymatic dissolution and size, count, morphology, and viability were assessed using Calcein-AM/PI imaging. Additionally, single administration of Kybella (500Ál) or Latanoprost (1.5 or 150mcg) was performed in vitro to murine fat pads and maintained 2-weeks. These samples were harvested and evaluated via H&E, Pentachrome to assess inguinal fat volume, and fibrotic tissue architecture. Samples were further interrogated via immunofluorescence against Perilipin, Hypoxia Inducible Factor 1-alpha (Hif1a), Uncoupling Protein 1 (UCP1), and hexokinase 2 to assess the variable contributions of Latanoprost therapy to white/brown adipose ratio, focal hypoxia, and metabolic flux.
RESULTS: Incubation of lipoaspirate with Kybella resulted in total tissue dissolution and loss of viability. In contrast, Latanoprost did not negatively affect viability of stromal cells or adipocytes. In vivo, both 150 mcg Latanoprost and Kybella significantly decreased inguinal fat pad volume at 2-weeks. Kybella treatment resulted in consistent dermal lesions and histologic evidence of inflammation that were not present in Latanoprost treatment. Furthermore, Latanoprost and vehicle-control treated samples did not significantly vary in presence of fibrotic collagen, Hif1a activation, or presence of UCP1-positive brown fat.
CONCLUSION: Single administration of soluble Latanoprost safely reduced fat pad volume at two weeks post injection in vivo with no ex vivo loss of viability in human tissues. This supports a potential application for reduction in focal adiposity without undesirable cytolysis and future studies will be conducted to optimize dose and determine duration of the effect.


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