recycling mechanisms, the proteasome and autophagy, were increased by TTC application (Figure 1D, E).
Next, TTC was also evaluated on ex vivo human abdominal skin (from a 34-year-old female, Fitzpatrick skin type II), which included hypodermis with adipose tissue. Similar to what was observed in the in vitro 3D model, TTC induced the expression of collagens (Figure 2A). Adipose markers of a thermogenic phenotype (UCP1 and TMEM26), adipokines (LEPT and ADIPOQ), and regulators of adipocyte function (SHOX2 and PPARG) were all increased with TTC application (Figure 2B). While lipogenesis targets were upregulated by TTC, this was matched by a larger increase in lipolytic genes (Figure 2C, D).
DISCUSSION
An ideal topical body contouring agent would simultaneously address multiple etiologies that affect skin quality. The primary goal of this report was to provide rationale and pre-clinical evidence for the bioactivity of a multimodal topical product intended to firm and rejuvenate skin, by boosting various ECM and DEJ components as well as supporting systems that promote lymphatic vessel quality, anti-inflammatory responses, cellular clearance and recycling, and adipocyte metabolism. Using a select gene panel in two different skin models, it was demonstrated that TTC can produce biological effects that are consistent with skin health, maintenance, and repair. Upregulation of ECM-associated genes in both models suggests that TTC stimulates dermal ECM component synthesis and improves ECM integrity (Figure 1A, 2A). VEGFC, a driver for lymphangiogenesis, was also upregulated by TTC which may translate into enhanced lymphatic drainage (Figure 1B). Rebalancing pro-inflammatory and anti-inflammatory cytokines, as was observed with TTC, can promote overall skin health (Figure 1C). In addition, key proteasome and autophagy related genes were also induced, indicating stimulation of cellular recycling mechanisms (Figure 1D, E). Finally, when TTC was applied on ex vivo skin containing adipocytes, changes in gene expression were observed that reflect an increase in adipocyte function and a metabolic state favoring lipolysis over lipogenesis (Figure 2B-D). In summary, these results indicate that TTC may benefit overall skin quality and aesthetic.
Comprehensive treatments for skin quality require that all components of the skin be considered since virtually every aspect of skin biology is affected by aging.3 The dermal microenvironment is highly vascularized, allowing fluids, nutrients, and immune cell traffic to maintain proper homeostasis. The cutaneous microvasculature declines with age, and it is proposed that improving the quality of blood and lymphatic vessels can support skin rejuvenation. Since cellulite etiology involves interstitial fluid buildup, the benefits of improving the lymphatic microvasculature can be twofold; restoring dermal homeostasis as well as facilitating fluid drainage and metabolite export from the enlarged fatty pockets in cellulite. In sum, TTC targets multiple biological pathways that can influence skin appearance; thus, it can be applied to multiple skin concerns.
Because keratinocytes and fibroblasts make up much of the skin, other cell types such as local dermal adipocytes have been largely overlooked. Considering recent findings that enlarged dermal adipocytes can affect the function of fibroblasts, coupled with the large potential for paracrine signaling through the plethora of secreted “adipokines,†modulation of this depot may have dramatic implications for overall skin quality beyond cellulite and cosmetic fat reduction.5,6
While this study only looked at gene expression using in vitro and ex vivo skin, the encouraging results provide impetus to evaluate TTC in randomized and controlled clinical studies that may uncover synergies from each pathway unable to be observed or measured in the employed test systems. For example, lymphatic circulation can help clear released free fatty acids from the tissue and prevent re-uptake. Lymphatic vessels are also heavily involved in the regulation of inflammation
Comprehensive treatments for skin quality require that all components of the skin be considered since virtually every aspect of skin biology is affected by aging.3 The dermal microenvironment is highly vascularized, allowing fluids, nutrients, and immune cell traffic to maintain proper homeostasis. The cutaneous microvasculature declines with age, and it is proposed that improving the quality of blood and lymphatic vessels can support skin rejuvenation. Since cellulite etiology involves interstitial fluid buildup, the benefits of improving the lymphatic microvasculature can be twofold; restoring dermal homeostasis as well as facilitating fluid drainage and metabolite export from the enlarged fatty pockets in cellulite. In sum, TTC targets multiple biological pathways that can influence skin appearance; thus, it can be applied to multiple skin concerns.
Because keratinocytes and fibroblasts make up much of the skin, other cell types such as local dermal adipocytes have been largely overlooked. Considering recent findings that enlarged dermal adipocytes can affect the function of fibroblasts, coupled with the large potential for paracrine signaling through the plethora of secreted “adipokines,†modulation of this depot may have dramatic implications for overall skin quality beyond cellulite and cosmetic fat reduction.5,6
While this study only looked at gene expression using in vitro and ex vivo skin, the encouraging results provide impetus to evaluate TTC in randomized and controlled clinical studies that may uncover synergies from each pathway unable to be observed or measured in the employed test systems. For example, lymphatic circulation can help clear released free fatty acids from the tissue and prevent re-uptake. Lymphatic vessels are also heavily involved in the regulation of inflammation
