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Abstract

Phototherapy was applied to treat medical conditions since 3,500 years, when the ancient Egyptians and Indians used sunlight to treat various diseases. It was only with the invention of electric light in the late 19th century that an alternative emerged. From that time on, the use of phototherapy in the medical field grew, techniques were perfected and developed and eventually gained widespread acceptance. To date, over 2000 scientific articles have been published in PubMed focusing on the various physiological effects of red and NIR radiation. These wavelengths of light have been shown to penetrate through human tissues and to locally and systematically influence cell metabolism, cell signalling, inflammatory processes and growth. This treatment is now called "photobiomodulation" (PBM) therapy. Despite the numerous studies reported, variability in irradiation settings and parameters has led to inconsistent outcomes. The greatest lack of knowledge is related to the effects of low wavelengths of blue/green light. Compared to red/NIR light, blue light is used for a limited range of medical applications because of its inhibitory and cytotoxic effects. However blue light effects have rarely been reported in adipogenesis or lipogenesis studies on adipose tissue. Hence, the biomodulatory potential of blue light at 453 nm wavelength was tested on 3T3-L1 cells during and after the differentiation process with respect to adipogenesis/lipogenesis, metabolic processes, cell proliferation and transcriptome changes. PBM using blue light revealed dose dependent effects during preadipocytes 3T3-L1 differentiation. A single irradiation performed at the first day of induction (Day0) led to a slight effect with a reduced lipid accumulation and changes in the expression of adipogenic markers that appeared down-regulated already after one exposure. Also metabolism, reflecting mitochondria activity, was negatively affected by blue light since oxidative phosphorylation and ATP contents were decreased with effects that were long lasting until 24h. Tests with repeated irradiations for all differentiation period showed an enhanced inhibition in lipid accumulation and metabolism. This chronic exposure was supposed to rise the ROS amount leading to DNA damages that have had as consequence a cell cycle delay, reduced proliferation rate and cell death processes. Gene expression analysis supported this hypothesis by an up-regulation of the p53 pathway and for all the other genes involved in repair systems such as ATM, Chk1 and Claspin. The blue light spectrum, being close to the harmful UVs wavelength, seems to induce cell death mediated by oxidative stress and damages accumulation in differentiating preadipocytes. On the other hand mature adipocytes treated with 21.6 j/cm2 or 43.2 j/cm2 of blue light have proven to be less responsive. No significant differences were reported in metabolism, growth and lipid storage. Similarly apoptosis has not been deregulated and no changes in ROS levels or cellular damages have been observed. In conclusion adipocytes seem to be more sensitive to blue light exposure during early rather than in late differentiation phases. Furthermore, the high doses of irradiation chosen led to inhibitory effects on metabolism and differentiation promoting cell death in preadipocytes subjected to chronic exposure while no effects were recorded in irradiated mature adipocytes. The results indicated that an optimal choice of irradiation parameters, particularly the dose or irradiation time, is important. Too high doses can lead to expected inhibitory but also deleterious effects on cells. Though inhibitory effects in adipogenesis or proliferation are requested relating to the treatment of hyperplastic obesity or dysregulation of lipid accumulation during childhood, the formation of aberrant cells has to be avoided. Therefore additional studies are needed to promote or reject blue light application in these fields. If tetraploid or aneuploid cells formation is not observed, blue light could be a possible alternative to pharmacological or surgical solutions in some obese subjects. However, there is currently no evidence of a possible application in hypertrophic obesity condition.