Non-Surgical Fat Reduction and Topical Modulation of Adipose Tissue Physiology openaccess articles

April 2019 | Volume 18 | Issue 4 | Original Article | 375 | Copyright © 2019

Alan D. Widgerow MBBCh MMed FCS(Plast) FACS,a Suzanne L. Kilmer MD,b John A. Garruto BS,c W. Grant Stevens MD FACSd

aUniversity of California, Irvine; Alastin Skincare, Inc., Carlsbad, CA bLaser and Skin Surgery of Northern California; University of California Davis Medical Center, Dept of Dermatology, Davis, CA cFree Radical Technology, Inc, Oceanside, CA dUSC Keck School of Medicine, Division of Plastic Surgery, Los Angeles, CA; Marina Plastic Surgery and MedSPA, Marina Del Rey, CA

Abstract

Non-surgical fat reduction procedures have gained in popularity over the past few years and remain in great demand. The process results in accumulation of breakdown products, lipid droplets, that are slowly absorbed over a period of months. This paper outlines the physiological process whereby lipid droplets are absorbed through a process of autophagy (lipophagy) involving a repackaging of these droplets to smaller sizes so that macrophages can then cope with digestion of these very large particles. Furthermore, a fat compartment is described within the dermis surrounding the tail of the hair follicle, which is attracting much attention due to its unique phenotype, function, and connection to the deeper subcutaneous fat compartment. This provides an entry route for direct signaling to the subcutaneous fat. Related to these novel concepts, peptides can be designed in liposomal delivery systems to target lipid droplet breakdown via the hair follicle entry route. This concept is elucidated in this paper.

J Drugs Dermatol. 2019;18(4):375-380.

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INTRODUCTION

Body sculpting and non-surgical fat removal procedures have become increasingly popular over the past few years. Non-invasive fat removal technologies include low level laser therapy, infrared light, ultrasound, radiofrequency, and cryolipolysis.1 Non-invasive body contouring procedures can be classified by the energy source deployed or the effect on the fat tissue, that of short term metabolic size reduction or long term permanent fat cell death.2 The latter process is more commonly chosen with fat cell destruction occurring in a number of ways: thermal necrosis following high frequency focused ultrasound; pulsed focus ultrasound that cavitates adipose tissue non-thermally; cryolipolysis that causes cold associated cellular apoptosis; and radiofrequency induced electroporation of the fat cell membrane.2 In addition, injectable lipolytic agents may also be used to decrease smaller fat tissue volumes. In all the above-mentioned processes, the adipose cell is damaged to differing degrees and varying degrees of inflammation ensue, however, in all, the content of the adipocyte, the lipid droplet, is released into the extracellular space to be slowly absorbed by macrophages over ensuing weeks or months.It is this process that deserves further attention – defining the mechanism of cellular destruction, examining the process of waste product/lipid droplet elimination, and seeking potential access routes for topical products which may optimize resolution of programmed fat tissue destruction.

Pathophysiology of Fat Reduction Processes

Radiofrequency (RF)Changes in the cellular structure following fat tissue exposure to RF has been termed pyroptosis. This relates to the focal delamination of the cell membrane seen in adipocytes approximately 2 weeks following RF exposure. This is followed by tears in the cell membrane with multiple pores evident, large enough for lipid droplets to pass through resulting in a reduction in adipocytes. This irreversible electroporation of the adipocyte cell membrane results in significant volume loss and cell death over a number of weeks.2CryolipolysisProgrammed, silent (non-inflammatory) cell death is the purported mechanism of action accompanying cryolipolysis. The theory is based on greater susceptibility of lipid filled adipocytes to cold as opposed to other water filled cells.3 However, there are current disputes around the non-inflammatory nature and cell wall disruption claimed with cryolipolysis.2,4 In addition, crystallization and cold ischemic injury of adipocytes inducing subsequent apoptosis (inflammatory, not silent) is also a suggested mechanism of action.5,6Ultrasound induces multiple pores and even rupture of the cell membrane and plasma membrane surrounding the lipid vacuole by cavitation. This allows leakage of triglyceride droplets from the droplet into the extracellular space.7

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