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Avci et al. Page 4 increased ROS levels following LLLT initiate a process known as lipid peroxidation where ROS reacts with lipids found within the cellular membranes, and temporarily damages them by creating pores [22,57–59]. However, in an attempt to replicate Neira et al.'s data [24], Brown et al. [23] failed to visualize any transitory micropores. In another study, Medrado et al. investigated the action of different fluences (9 mW, 670 nm, 4, 8, 12, and 16 J/cm2 for 31, 62, 124, and 248 seconds, respectively) from a gallium–aluminum arsenide laser which was applied through the intact skin to the dorsal fat pad of rats. LLLT caused brown adipose fat droplets to coalesce and fuse, apparently transforming them into yellow fat but had only negligible effect on yellow fat itself [60]. Increased vascular proliferation, mitochondria, and congestion were evident findings in the laser irradiated brown fat. Considering most changes were restricted to the brown fatty tissue only and yellow tissue always preserved its appearance with no signs of lipolysis observed, results from this study were not in accordance with Niera et al.'s study. However, it is worthwhile to mention that experimental parameters used in these studies were not the same. Another possible mechanism of action for release of lipids was proposed to be through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids [29]. To investigate the complement activation theory, Caruso-Davis et al. [29] exposed differentiated human adipocytes to plasma. With and without irradiation there was noted to be no difference in complement induced lysis of adipocytes. Although no enzymatic assays were done to determine levels of complement within the plasma, the group concluded that laser does not activate complement. Lastly, unlike Niera et al.'s [60] findings, the external cell membrane preserved its normal appearance in electron microscopy, presenting no ruptures nor pores, in spite of the disposition of its fused fatty vacuoles, and no other signs of lipolysis were observed. An additional paper called into question the ability of red light (635 nm) to penetrate effectively below the skin surface and into the subdermal tissues [61]. In a supportive commentary Peter Fodor stated; “One could postulate that the presence of the black dots on SEM images on the surface of fat cells reported by Neira et al. could represent an artifact” [23]. It is also possible that LLLT stimulates the mitochondria in adipocytes that in turn leads to an increase ATP synthesis with subsequent upregulation of cAMP [62–65]; the increased cAMP could activate protein kinase which could stimulate cytoplasmic lipase, an enzyme that converts triglycerides into fatty acids and glycerol, which can both pass through pores formed in the cell membrane may cause a shrinkage in adipocytes [30,66] (see Fig. 5). However, Caruso-Davis et al. findings from in vitro studies on human fat cells obtained from subcutaneous fat, irradiated with 635–680 nm LLLT for 10 minutes demonstrated no increase of glycerol and fatty acids suggesting that fat loss from the adipocytes in response to laser treatment was not due to a stimulation of lipolysis, however they did detect increased triglyceride levels which further supported the formation of pores in adipocytes [29]. Figure 6 graphically illustrates many of the proposed mechanisms that have been devised to explain the use of LLLT for fat removal. LLLT FOR NONINVASIVE BODY CONTOURING The Zerona LipoLaser (Erchonia Medical, Inc.) is a device with five rotating independent diode laser heads each emitting 17 mW of 635 nm laser light (Fig. 3B). It was the first noninvasive aesthetic device to receive FDA market clearance in the US for circumferential reduction of the waist, hips, and thighs following completion of a placebo-controlled, randomized, double-blind, multisite clinical investigation evaluating 67 study participants [67]. The results obtained from that study demonstrated an average reduction of 3.51 inches across patient's waist, hips, and thighs in as little as 2 weeks. The clinical trial, absence of diet restrictions, exercise requirements, or any other adjunctive components properly Lasers Surg Med. Author manuscript; available in PMC 2014 August 01. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptPDF Image | Low-Level Laser Therapy for Fat Layer Reduction
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