Mamofillin New aesthetic perspective

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1 New aesthetic perspective

2 White adipose tissue (WAT) White adipose tissue (WAT) is the prevalent type in human adults functioning as the major storage site for the lipids absorbed from daily intake (triglycerides and cholesterol esters), which are burned whenever body cells require energy. Adipocytes and preadipocytes are the main cells in WAT, this tissue also contains macrophages, fibroblasts, leukocytes and many collagen fibers, which provide structural support. WAT volume can vary depending on the number of adipocytes and their size, parameter that increases along with lipid accumulation. The number of mature adipocytes with capacity to store lipids can rise due to the differentiation process, which transforms preadipocytes into mature adipocytes. This maturation is a complex process known as adipogenesis, in which Peroxisome Proliferator-Activated Receptor-Gamma (PPARɣ) and Peroxisome proliferator-activated receptor-gamma Coactivator 1 alpha (PGC-1α) are both indispensable. Adipose tissue Adipocyte Nucleus and cytoplasm Store lipids info@

3 Adipogenesis Adipogenesis is a complex process in which many factors and genes interfere. Some genes must be expressed as they are distinctive of mature adipocytes while the typical genes of preadipocytes need to be downregulated to finally lead to the adipocyte phenotype. The Peroxisome proliferator activated-receptor Gamma Coactivator-1 alpha (PGC-1α) is a transcriptional coactivator that interacts with a broad range of transcriptional factors and nuclear receptors (including PPARɣ). PPAR belongs to a family of nuclear receptor proteins that functions as transcriptional factors and regulates gene expression in cellular differentiation among other processes. This receptor forms heterodimers with Retinoid X Receptors which bind to specific regions on the DNA of target genes and regulate their expression. PPARɣ is predominantly expressed in the adipose tissue and it is strictly necessary but not sufficient for the differentiation of preadipocytes. PGC-1α is a transcriptional coactivator that interacts with a broad range of transcriptional factors and nuclear receptors (including PPARɣ), increasing the probability of certain genes related to adipocyte differentiation being transcribed. PGC-1α PPARγ PGC-1α PPARγ info@

4 PPARɣ / PGC-1α It was observed that a robust induction of PGC-1α expression during ex vivo human subcutaneous preadipocyte differentiation in WAT, had a level as high as in mature adipocytes. It was confirmed that in WAT, PGC-1α interacts with PPARɣ potentiating the expression of relevant genes related to adipocyte differentiation, thus stimulating adipogenesis. PGC-1α MBE IRSs Thus, stimulating or reducing PGC1α expression would increase or diminish adipocyte maturation and, therefore, the number of adipocytes capable of storing lipids. The total number of white adipocytes is normally constant throughout adult life. gene CRE Thus, a modulation of the differentiation process would alter the equilibrium between adipocyte maturation and death rate, and hence increase the amount of mature white adipocytes. PGC-1α PPARγ PGC-1α PPARγ adipogenesis info@

5 Skin Tech innovation New cosmetic ingredients targeting adipogenesis become a key solution for increasing or reducing fat tissue volume in localised areas. Acetyl Hexapeptide-38 is a new hexapeptide that induces PGC-1α expression, and thus, stimulates adipogenesis, leading to an increase in lipid storage in preadipocytes which boosts fat tissue volume, for both anti-ageing and volume enhancing formulations. INSULIN CALCIUM AMP GLUCAGON AMPK camp CaMKIV PKA MEF2 FoxO CREB PGC-1α gene Acetyl Hexapeptide-38 MBE IRSs CRE info@

6 In vitro study: Acetyl Hexapeptide-38 increased the expression of PGC-1α by 25.6% The efficacy of Acetyl Hexapeptide-38 was studied by quantitative realtime PCR to determine the effects on PGC-1α expression. The differentiation of pre-cultured subcutaneous human preadipocytes was induced with preadipocytes differentiation medium (PDM-2). Acetyl Hexapeptide-38 (0.1 mg/ml) was added during differentiation, and all samples (including control ones) were incubated at 37ºC during 10 days. Then cells were lysed and expression of PGC-1α was measured by quantitative RT-PCR. The addition of 0,1mg of Acetyl Hexapeptide-38 increased the expression of PGC-1α by 25.6%. These results demonstrate that the expression of PGC-1α is increased in the samples treated with Acetyl Hexapeptide-38 in comparison to control samples.

7 In vitro study: Effect on Lipid Accumulation in preadipocytes The effect of Acetyl Hexapeptide-38 on lipid accumulation was quantified by AdipoRed assay. Human subcutaneous preadipocytes were incubated at 37 C for 24 hours in PGM-2 (Preadipocyte Growth Medium-2), which was subsequently changed to PDM-2 to induce adipogenesis. Cells were then incubated for 10 days in presence of Acetyl Hexapeptide-38. PDM-2 was used as a negative control and PGM-2 as a basal control. After 10 days of incubation, the accumulation of intracellular triglycerides using the AdipoRed assay reagent was measured. The supernatants were removed, wells were washed and 5µL of AdipoRed reagent was added. After 15 minutes at room temperature, fluorescence was measured with an automated multiplate fluorescence reader set for excitation at 485nm and detection at 535nm. The AdipoRed reagent facilitates the detection of intracellular lipid droplets as it is a hydrophilic solution that turns into fluorescent in hydrophobic environments. According to test results, Acetyl Hexapeptide-38 demonstrated increased lipid accumulation by 27.9%, compared to non-treated differentiated cells in adipocytes coming from preadipocytes treated with this peptide. info@

8 In vivo study: breast volume increase For the evaluation of the in vivo efficacy of Acetyl Hexapeptide-38 in increasing breast local volume, a panel of 22 females (25-40 years old) with a European bra cup size between 80 and 90 was selected. They applied the placebo cream in a breast and the cream with Acetyl Hexapeptide-38 in the other, twice a day for 56 days. Measurements of breast volume were taken at the beginning and at day 14, 28 and 56 using the Fast Optical In vivo Topometry Technique (FOITS), which allows reconstructing the surface and the volume of the breast based on the principle of optical interferometry. The relative volume of the area and different 3D images were obtained, calculating the differences in mm 3 versus the initial time, as well as the evolution of the breast volume. Results & Conclusion Acetyl Hexapeptide-38 demonstrated to be a volume booster ingredient that can increase local volume and revert aging-induced volume losses, making it essential in replenishing formulations, body shaping and anti-aging treatments. References 1. Petrofsky J, Prowse M, Lohman E. The influence of ageing and diabetes on skin and subcutaneous fat thickness in different regions of the body. The Journal of Applied Research. 8 (1): 55-61, Quatresooz P, Xhauflaire-Uhoda E, Piérard-Franchimont C, et al. Cellulite histopathology and related mechanobiology. International Journal of Cosmetic Science. 28: , Tchkonia T, Morbeck DE, Zglinicki T., et al. Fat tissue, aging, and cellular senescence. Aging Cell. 9: , Liang H, Ward WF. PGC-1α: a key regulator of energy metabolism. Adv Physiol Educ. 30: , Semple RK, Crowley VC, Sewter CP, et al. Expression of the thermogenic nuclear hormone receptor coactivator PGC-1α is reduced in the adipose tissue of morbidly obese subjects. International Journal of Obesity. 28: , info@

9 mamofillin cream Contents: Acetyl Hexapeptide-38 Glycolic Acid Emmolents mamofillin milk Contents: Acetyl Hexapeptide-38 Glycolic Acid Emmolents Higher efficacy of the cream compared to milk due to a higher concentration of active ingredient (2,5 times) Higher viscosity Long term contact with skin during period of application Recommendation: Night Low viscosity & quickly absorbtion Not greasy & not sticky, easy to use Recommendation: Morning info@

10 Indications - Breast volumizing at any age, or after pregnancy and breast feeding - Breast asymmetry - Reduced breast impact after diet or starvation - Fragile skin and wrinkles on the decoltage Contraindications - Open wounds - Skin infections Instructions for use Application of cream/milk by using smooth massages 2 times a day on the clean skin info@

11 Clinical efficacy First 3 weeks of application First contact of Acetyl Hexapeptide-38 with preadipocytes by chain signal molecules Skin: soften Volume : no change From 3 rd to 6 th week of application Start preadipocytes volumizing From 6 th to 9 th week of application Breast volume increase Visible push up effect Main recommendation: Maintenance of the results by continuous application Volume could progressively decrease, in case of stopping application of cream /milk info@