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Pyroptosis of Fat DR DIANE DUNCAN Discusses the Bodyfx Treatment and How Cell Death Mechanisms Affect Clinical Results

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Pyroptosis of Fat DR DIANE DUNCAN Discusses the Bodyfx Treatment and How Cell Death Mechanisms Affect Clinical Results 54 EQUIPMENT I body language Pyroptosis of fat DR DIANE DUNCAN discusses the BodyFX treatment and how cell death mechanisms affect clinical results hen we talk about have programmed cell death we ways to destroy fat, would be massive creatures. we loosely use the By definition there’s no inflam- Wterms necrosis and mation at all when an apoptotic apoptosis because these are the process occurs. mechanisms that are most com- Necrosis, on the other hand, monly known. Here I’d like to is severely inflammatory, but it is highlight the importance of bear- not the ideal mechanism for fat ing in mind the particular way in reduction either. Necrosis causes which a cell dies. Consideration an instant demise of the affected of how the cell dies and how this cell. The cell membrane ruptures, mechanism of death will affect the causing the release of lysozymes clinical outcomes is an important into the surrounding tissue and the and somewhat overlooked premise. involved cells undergo significant swelling. Another word for the pro- Ways to kill fat cess is “oncosis”, as necrosis is more Until recently we’ve only thought correctly used as identifying the of the two polar opposites of ways cell when it is dead. to kill fat. Apoptosis is really silent cell death and this is what happens Necrosis and apoptosis when our cells die in order keep Why is neither necrosis nor ap- the total population of cells stable. optosis an ideal mechanism when About 100,000 cells per second contouring the face, neck, or body? undergo apoptosis in a human be- In apoptosis there is no inflam- cause our cells also divide and un- mation, and in necrosis, the swell- has a thick, sturdy fibrovascular dergo mitosis. A balance must be ing and bruising cause significant network that holds the fatty layer kept. As you know embryos tend to down time. Controlled inflamma- together and binds it to the under- have a tail, and it’s apoptosis that tion is desirable, as with time, the lying fascia and overlying skin. A makes the cells of that tail disap- body loses its support system for 44 year old has lost about 50% of pear without a scar. If we didn’t soft tissue (figure 1). A 23 year old this support network, allowing re- gions of fat to become pendulous and quite saggy. By age 60, about CELL DEATH 85% of the fibrous tissue binding Apoptosis is a normal, always ongoing process in humans that programs fat cells together has eroded away. cells to die in order to offset the number of new cells created by mitosis. When we use the term “skin lax- Necrosis is immediate, sudden, and very inflammatory, so patients treated ity”, we are actually talking about with a necrosis inducing regimen—such as injection lipolysis—will see a lot a combination of the skin and adi- of swelling and bruising. Both necrosis and pyroptotic-like mechanisms are pose layer. The loss of attachment pro-inflammatory. One has poration and one does not. One has cell shrink- to the underlying fascia, plus the age and one is characterized by cell wall rupture. loss of a scaffold that is knitting Apoptosis and necrosis are not the only mechanisms of cell death; others the fatty layer together, cause the include autophagy, pyroptosis, caspase independent apoptosis, paraptosis, flabby character of ageing skin Wallerian degeneration, cornification and anoikis. and soft tissue. In many cases, the nature of the soft tissue is actu- BL77.indd 54 25/11/2015 15:58 body language I EQUIPMENT 55 scar tissue formation. A desired outcome would be restoration of the youthful fibro- vascular support system to the adipose layer. This would require a fractional and somewhat uni- form response—layers of tendrils of collagen that are interspersed 23 years old within the fatty layer. A multilevel response would be needed, and the response would need to be able to be controlled—more fibrous sup- port in some areas, like the jowl or lower abdomen and a bit less in areas that do not tend to be pendu- lous, like the cheek, or outer thigh. The fibrous support response alone 44 years old can be generated with a moving external radiofrequency device like Forma or Plus. Results and temperature I did a study in which I looked at serial scanning electron microsco- py sections of fat, treated over time 60 years old with Forma at different maximum Figure 1: Young adipose tissue has a strong fi- temperatures: 40, 41, 42, and 43 brovascular support framework. Middle aged degrees Celsius. We looked at adi- tissue has lost part of the binding and struc- tural tissue. Older tissue has retained very little pose cells immediately following remaining connective tissue, allowing the soft the eighth weekly treatment, at one tissue to appear lax and pendulous month following treatment cessa- tion, and again at three months fol- ered, and no fat death was noted lowing treatment cessation. We had with Forma treatments. two questions: one, could moving Contrary to the belief that bulk RF alone kill fat? And two, does a heating, especially radio frequency hotter temperature which may not bulk heating, doesn’t work, I have be well tolerated by the patient cre- proof that it does. However, the ate a better tissue response? Figure level of fibrous ingrowth into the 2 shows a matrix of SEMs showing adipose layer did not vary as sig- tissue response over time at differ- nificantly with temperature level ent temperatures. Temporary cell as originally thought. We’ve been deformation increases with higher instructed to get the tissue as hot ally more important than that of temperatures. If you read the ther- as possible, however even at 40 de- the skin. mal literature, fat must get to about grees, there was a significant tissue 55 degrees Celsius in order to cause response in treated areas. Patients Soft Tissue Contouring necrosis. It is extremely difficult to tend not to come back to repeat The ideal mechanism for soft tissue create that level of heat transcuta- painful experiences. Clinical re- contouring would be somewhere neously with external RF alone. In- sults are just as good with lower between apoptosis—with no in- terestingly, at one month and three temperatures and longer treatment flammation, and necrosis’ rampant months, all adipocytes had recov- times. 40 41 42 43 Figure 2: Effect of temperature difference on fibrous tissue response at three months post treatment with moving external RF only. All tissue has fibrous and vascular in- growth. More cell deformation is present at 43 degrees. If tissue support and molding is the goal, keeping the temperature at 42 degrees or below may be best, as a small amount of fat may die at higher temperatures. BL77.indd 55 25/11/2015 15:58 56 EQUIPMENT I body language Repeated Measures Before treatment Mean/ SD After 1 month Mean/ SD After 3 months Mean/ SD ANCOVA US @ 0 degrees 2.63+/- .283 1.74 +/- .202 1.68 +/- .218 US @ 90 degrees 2.83 +/-.160 1.57 +/- .164 1.55 +/- .188 Figure 3: High reso- lution ultrasound US @ 180 degrees 2.60 +/- .249 1.71 +/- .184 1.76 +/- .204 fat thickness meas- US @270 degrees 2.82 +/- .237 1.49 +/- .150 1.57 +/- .179 urements Multi- variate ANCOVA : * p=<.05 The standard for statistical significance 53.25% fat thick- **p=<.001 Stronger statistical significance ness reduction at three months post The repeated measures analysis (ANCOVA) has been adjusted for age and height last treatment Tissue tightening and fat The importance of death lowers the poration threshold. It reduction over time doesn’t really cause induction of fat A device like BodyFX also has Most people understand that the death—we treat anywhere between moving external radiofrequency. inflammatory process in humans 40°C and 43°C—but it does cause The handpiece is suction-cou- takes time. There is about a six- the induction of fibrous response. pled, which means that the target week healing process after surgery Different devices that claim fat loss tissue is firmly held so that heat and the strength of the repair of a with only moving RF are not very can better get to it. The depth of surgical incision gains about 10% likely to work, given this research. energy penetration is also con- per month. This is a process that I’ve done a lot of scanning of what trolled this way. However, the cannot be hurried. If adipose cells happens when tissues are heated secondary electrical impulse is die over time, there is no discom- using scanning electron micros- the secret ingredient that makes fort, no swelling, no bruising, and copy, SEM, which is much easier the fat die. no down time. With simple exter- for people to understand than his- One of the recent advances in nal RF heat, the pattern of fibrous tology. Adipocytes are notoriously medicine is reversible electropo- infiltration has barely begun at difficult to fix and cut in histologic ration, which is used to introduce the end of the eighth treatment, sections as the cells can easily frac- small molecules into a cell, cause is stronger one month following ture with processing. The SEM cell fusion, or enable genetic al- treatment cessation, and has be- doesn’t have those artefacts. What teration. This causes temporary come quite visible at three months. you see with electron microscopy relaxation of the pores in the A similar process is seen with the cannot be manipulated. cell membrane of target cells, so Body FX; fat takes at least three Using an SEM I have studied that medicine or other “genetic months to optimally remodel.
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