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Perilipin, The Lipid Droplets’ Bodyguard, as a Target for Silhouette Refining
Stefan Bänziger PhD, Manager Development Cosmetic Actives, RAHN AG, discusses strategies to fight problematic areas of the body and points to the important role that the fat-protecting protein Perilipin plays in the management of these areas
Excessive fat deposition in Adipocytes is not only the major cause of obesity but also significantly contributes to problematic areas of the body leading to cellulite, orange peel, love handles, and excess centimetres on waistline. Body fat is stored in lipid droplets. The lipid droplet- associated protein Perilipin is a critical regulator of fat storage and mobilisation. In the basal state, Perilipin forms a protective barrier on lipid droplets restricting the access of lipid-degrading Lipases. Perilipin thereby maintains a low rate of constitutive fat degradation (Lipolysis) and promotes fat storage (Lipogenesis). Upon stimulation, in contrast, Perilipin promotes fat degradation by re-shaping lipid-droplet structure and by facilitating the access of Lipases to lipids. Outsmarting Perilipin may thus represent the long- awaited key to effortless weight loss. Cosmetic intervention strategies against problem
areas, however, generally aim to 1) control lipid storage in order to reduce fat mass. This is achieved by activating Lipolysis, deactivating Lipogenesis, or preventing Adipocyte differentiation, which is the maturation of Pre-adipocytes into Adipocytes; 2) activate microcirculation in order to improve
lymphatic drainage and lipid clearance; 3) tighten the skin surface in order to reduce the appearance of dimples and general unevenness. RAHN’s cosmetic active SLIMEXIR®
contains X-Melt®
(a synergistic blend of Methylxanthines), Artichoke extract, and the polysaccharide Levan: X-Melt®
and Artichoke extract stimulate
prevents fat uptake by reducing Adipocyte maturation. In addition, each component activates Lipolysis, which triggers decomposition of existing fat. X-Melt®
cutaneous microcirculation and facilitate the transport of decomposed lipids. Furthermore, Levan provides a tightening skin effect. We hypothesise that SLIMEXIR®
may partly mediate its effect by inducing
lipid-dropled re-modelling via Perilipin activation. SLIMEXIR®
prevents Adipocyte
maturation and fat storage During differentiation, 3T3-L1 Pre-adipocytes were incubated with X-Melt®
SLIMEXIR® . After 6 days morphology and
lipid accumulation were determined by microscopy using Sudan-II staining. X-Melt®
≥ 0.005% prevented
Adipocyte maturation and reduced lipid accumulation by up to 90%. Due to its special composition X-Melt® outperformed the current reference substance Caffeine (Figure 1).
refines the abdomen in-vivo
Relative abdomen volumes of slightly overweight women were determined by fringe projection on days 0, 28, and 56 after application of a light test foam formulation containing 4% SLIMEXIR®
.
Significant effects were measured for 70% (28 days) and 73% (56 days) of the participants. Treatment caused a relative abdominal volume reduction of 0.7% (28 days) and 1.1% (56 days) (Figure 3).
Conclusion SLIMEXIR®
is a novel concept to fight the causes of
all problematic areas simultaneously, eventually leading to visible and measurable body-shaping effects. SLIMEXIR®
is easy to formulate and is
suitable for modern body care treatments comprising silhouette-refining or problem-area reshaping.
RAHN AG, Stand K71 SLIMEXIR® stimulates fat degradation - possibly
by Perilipin-mediated lipid-droplet remodelling Furthermore, all ingredients activated fat degradation (not shown here). Fat degradation is controlled via the content of the messenger substance cAMP. Elevated cAMP induces Protein Kinase A- and subsequent Perilipin activation. This has two effects: 1) lipid droplets fragment into thousands of tiny globules and, 2) Perilipin becomes a docking station for Lipases. We thus hypothesised that SLIMEXIR® may promote lipid degradation by activating Perilipin. Primary, 6h-SLIMEXIR®
-treated human Adipocytes
were investigated for Perilipin expression and lipid- droplet distribution by confocal microscopy. SLIMEXIR® treatment could induce lipid-droplet remodelling: lipid droplets broke apart and gradually dissolved (Figure 2).
Figure 2: SLIMEXIR® Figure 1: X-Melt® reduces fat accumulation
Fully differentiated Adipocytes have a spherical shape and are tightly packed with lipids (untreated). X-Melt®
-treated cells largely retained their pointed shape and barely stored lipids. The effects of Caffeine were less pronounced
induces lipid-droplet reshaping
Untreated cells showed large lipid globules - protectively enclosed by Perilipin. The activation of fat degradation (IBMX/ Isoprotenerol) induced lipid- droplet fragmentation and dissolution. SLIMEXIR® treatment displayed corresponding effects, although less pronounced. Please note, that this was a qualitative study only, aiming to illustrate the potential mechanism underlying fat degradation
Figure 3: SLIMEXIR®
Maximum reduction was 9% or 4.5cm3 average BMI=25.9, average age=38)
reduces abdominal volume (n=23,
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