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Title: A Polyglucuronic Acid to Target the FIAF Adipokine for Slimming Effects
cellulitex FIAF adipokinex slimmingx firmingx polyglucuronic acidx
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Keywords: cellulite | FIAF adipokine | slimming | firming | polyglucuronic acid

Abstract: Effective slimming actives should reduce lipogenesis, increase lipolysis, promote fatty acid release and improve skin firmness. Here, the authors describe the development of such an active based on polyglucuronic acid. Further, this material is shown to act on a new biological pathway involving the fasting-induced adipose factor (FIAF) adipokine.

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L Rios, C Delattre, P Patriarca, m Favre-Mercuret and J-Y Berthon, A Polyglucuronic Acid to Target the FIAF Adipokine for Slimming Effects, Cosm & Toil 126(3) 196 (2011)

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Today, cellulite is manifested in 80–90% of women but rarely in men. As is generally known, it appears as a modification of skin topography, evident by skin dimples. Cellulite appears regardless of a woman’s age, ethnic origin, body shape or weight; while weight gain can worsen its appearance, it can also be seen in slimmer women. Research has clearly shown that cellulite is a condition of increased adiposity as well as altered connective tissue. This cutaneous irregularity gives rise to structural changes in fatty layers and the surrounding matrix.1, 2

In women, the manifestation of cellulite is primarily caused by a combination of two factors: the lipidic deposit and the particular architecture of the subcutaneous tissue, where fibrous branches contained in the surrounding matrix that are perpendicular to the skin’s surface separate voluminous lobules of lipids into rectangular sections. The peaks press against the dermis and push outward, forming adipose lobes that appear mattresslike, an effect often likened to an orange peel. In contrast, in men, the bands of fibrous branches in the subcutaneous tissue take a different course: they crisscross and form smaller, polygon-shaped lobules that even in cases of lipidic hyper-accumulation are inclined to protrude toward the dermis.1, 2

Concerning the extracellular matrix of both women and men, the rarefaction of subepidermal collagens and elastic fibers are observed and a thick, hard collagen layer surrounds the adipocytes, constituting the micronodules of the cellulite. These phenomena all lead to a loss of elasticity and tonicity in the cutaneous layers. Thus, the skin appears much like a mattress and looks less smooth.

As research advances the development of ingredients that diminish this cutaneous modification, insight into adipocyte and extracellular matrix physiology has grown. In turn, ingredients have been developed to act directly on the destock of fats inside the adipose cells and also to improve the matrix properties.3 The present work describes a material designed to influence a new biological pathway involving the fasting-induced adipose factor (FIAF) adipokine.

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Table 1. Modulation by Polyglucuronic Acid of the Expression of Different and Specific Genes Involved in the Transport and the Metabolism of Lipids

Table 1. Modulation by Polyglucuronic Acid of the Expression of Different and Specific Genes Involved in the Transport and the Metabolism of Lipids

Results showed that the polyglucuronic acid modulated the expression of different and specific genes involved in the transport and metabolism of lipids (see Table 1).

Figure 1. The spatial conformation of the described polyglucuronic acid

Figure 1. The spatial conformation of the described polyglucuronic acid

A polyglucuronic acid was developed based on a specific polysaccharidea with a low molecular weigh of 400 kDa (see Figure 1).

Figure 2. Polyglucuronic acid activity on adipokine FIAF synthesis to enhance LPL inhibition; FA = fatty acids, LPL = lipoprotein lipase and TG = triglycerides

Figure 2. Polyglucuronic acid activity on adipokine FIAF synthesis to enhance LPL inhibition; FA = fatty acids, LPL = lipoprotein lipase and TG = triglycerides

As noted, the polyglucuronic acid was designed to simultaneously activate four targets; first, to induce adipokine FIAF synthesis by adipocytes to enhance the inhibition of the enzyme LPL (see Figure 2).

Figure 3. The transcriptomic method

Figure 3. The transcriptomic method

This technique utilizes DNA microarray to screen for the biological activities of 44,000 genes in the human genome (see Figure 3).

Figure 4. Morphological study of a) untreated and b) isolated adipocytes treated with 0.5% polyglucuronic acid by analysis of reduced red color intensity

Figure 4. Morphological study of a) untreated and b) isolated adipocytes treated with 0.5% polyglucuronic acid by analysis of reduced red color intensity

As Figure 4 shows, 0.5% polyglucuronic acid on the adipocyte culture reduced the amount of intracellular lipids by 26%, thus indicating the active decreases lipid storage.

Figure 5. Search for aP2/FABP4 protein by Western Blot in control sample cells and treated cells sample; detection was carried out by assessing protein ß-actine

Figure 5. Search for aP2/FABP4 protein by Western Blot in control sample cells and treated cells sample; detection was carried out by assessing protein ß-actine

Results demonstrated a lower expression of aP2/FABP4 in the treated cells (see Figure 5), indicating the polyglucuronic acid blocked pre-adipocyte differentiation to mature adipocytes.

Figure 6. Microscopic analysis of control pre-adipocytes and pre-adipocytes treated with 0.5% polyglucuronic acid

Figure 6. Microscopic analysis of control pre-adipocytes and pre-adipocytes treated with 0.5% polyglucuronic acid

To confirm the Western blot results, an additional Adipored study was carried out (see Figure 6).

Figure 7. Total collagen amount by measuring hydroxyproline using the phase inverse HPLC technique on fibroblasts treated or untreated with 0.5% or 1% polyglucuronic acid

Figure 7. Total collagen amount by measuring hydroxyproline using the phase inverse HPLC technique on fibroblasts treated or untreated with 0.5% or 1% polyglucuronic acid

Results indicated a significant increase in total collagen level, respectively by 21% and 30% (see Figure 7).

Figure 8. Amount of the total GAGs measuring the selectively of the fixed radioactive precursor ([3H]-glucosamine) on fibroblasts treated or untreated with 0.5% or 1% polyglucuronic acid

Figure 8. Amount of the total GAGs measuring the selectively of the fixed radioactive precursor ([3H]-glucosamine) on fibroblasts treated or untreated with 0.5% or 1% polyglucuronic acid

Fibroblasts in culture were treated with 0.5% and 1.0% polyglucuronic acid, and found to significantly increase the neosynthesis of total GAGs by 18% and 26%, respectively (see Figure 8).

Figure 9. Amount of integrin synthesis on fibroblasts treated or untreated with 0.5% or 1% polyglucuronic acid

Figure 9. Amount of integrin synthesis on fibroblasts treated or untreated with 0.5% or 1% polyglucuronic acid

Fibroblasts in culture treated with 0.5% and 1% polyglucuronic acid demonstrated significantly increased integrin synthesis, by 16% and 17%, respectively (see Figure 9).

Figure 10. Percentage evolution of volunteers whose clinical cellulite grade decreased from stage III (severe cellulite) to stage II (moderate cellulite)

Figure 10. Percentage evolution of volunteers whose clinical cellulite grade decreased from stage III (severe cellulite) to stage II (moderate cellulite)

Researchers subtracted the control result, i.e. the massage-only effect, from the perceived reduction in cellulite (see Figure 10), and results indicated that the 3% polyglucuronic acid formulation reduced the cellulite grade of volunteers.

Figure 11. Percentage evolution of volunteers whose clinical cellulite stage decreased from stage II (moderate cellulite) to stage I (light cellulite)

Figure 11. Percentage evolution of volunteers whose clinical cellulite stage decreased from stage II (moderate cellulite) to stage I (light cellulite)

In addition, the 3% polyglucuronic acid formulation decreased moderate cellulite (stage II) to light (stage I) in 25% of volunteers at day 15, and for 50% at day 30 (see Figure 11).

Figure 12. Centimetric measurements of thigh size on volunteers each week for eight weeks of twice daily use of a control and 1% polyglucuronic acid test formula

Figure 12. Centimetric measurements of thigh size on volunteers each week for eight weeks of twice daily use of a control and 1% polyglucuronic acid test formula

Thus, the polyglucuronic acid at 1% reduced the centimetric measurement of the thighs of volunteers aft er eight weeks of use of the test product (see Figures 12 and 13).

Figure 13. The cellulite of two volunteers before and after eight weeks of twice daily use of a control (left thigh) and b) 1% polyglucuronic acid test formula (right thigh)

Figure 13. The cellulite of two volunteers before and after eight weeks of twice daily use of a control (left thigh) and b) 1% polyglucuronic acid test formula (right thigh)

Thus, the polyglucuronic acid at 1% reduced the centimetric measurement of the thighs of volunteers aft er eight weeks of use of the test product (see Figures 12 and 13).

Footnotes (CT1103 Rios)

aTimiline (INCI: Polyglucuronic Acid) is a product of Greentech S.A.

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