Phenotypical Conversions of Dermal Adipocytes as Pathophysiological Steps in Inflammatory Cutaneous Disorders

Adipocytes from the superficial layer of subcutaneous adipose tissue undergo cyclic de- and re-differentiation, which can significantly influence the development of skin inflammation under different cutaneous conditions. This inflammation can be connected with local loading of the reticular dermis with lipids released due to de-differentiation of adipocytes during the catagen phase of the hair follicle cycle. Alternatively, the inflammation parallels a widespread release of cathelicidin, which typically takes place in the anagen phase (especially in the presence of pathogens). Additionally, trans-differentiation of dermal adipocytes into myofibroblasts, which can occur under some pathological conditions, can be responsible for the development of collateral scarring in acne. Here, we provide an overview of such cellular conversions in the skin and discuss their possible involvement in the pathophysiology of inflammatory skin conditions, such as acne and psoriasis

Modeling of the spatiotemporal distribution of temperature fields in skin and subcutaneous adipose tissue after exposure to ultrasound waves of different frequencies

Temperature fields produced in the skin and adjacent subcutaneous white adipose tissue (sWAT) during and after exposure to ultrasound (US) waves are significantly dependent on the US frequency. In this study, we present theoretical descriptions of temperature fields appearing in composite skin/sWAT after exposure to US at frequencies of 3 MHz, 10 MHz, and 19 MHz. While the temperature increased by approximately 1.5°C in skin during US exposure at intensities up to 10.0 W/cm2 and a frequency of 3 MHz, this increase reached 9.0°C and 16.0°C at US frequencies of 10 MHz and 19 MHz, respectively. Because of the large difference in heat capacitances and US attenuation coefficients in the skin and adjacent sWAT, the interface between these two layers was subjected to a temperature gradient that increased with US frequency. This gradient was low after applications of US at 3 MHz but was as high as 7.5°C/mm at 10 MHz and 14.0°C/mm at 19 MHz for US intensities of 10.0 W/cm2. High temperature gradients produced by US at the dermis/sWAT interface can significantly affect the adherence between these two layers and thus modulate effective mechanical properties of the skin

Influence of layered skin structure on the distribution of radiofrequency currents in dermis and subcutaneous fat

The layered structure of skin with multiple interfaces separating the skin layers having very different electrical characteristics significantly modifies the spatial distribution of radiofrequency (RF) current in the skin compared to that in a homogeneous medium. In this study we present the analytical solutions of Laplace’s equation describing the current densities for a two-layer skin model with homogeneous single layers for the monopolar and bipolar configurations of RF electrodes. Then we analyze analytically and numerically the optimal distances between the RF electrodes providing the maximal current concentration in a given depth or in a given depths’ interval under the skin surface. It is demonstrated that two main parameters which significantly define the optimization condition are the thickness of the dermis and the reflection coefficient of the current at the dermis/subcutis interface. According to this model, under physiological conditions, the surface under RF electrode collecting 50% of the current entering subcutis is 184 times larger than in homogeneous medium. Such redistribution of RF current will significantly reduce the local density of the current entering the fat tissue reducing the effect of its selective heating

Microstructural inhomogeneity of electrical conductivity in subcutaneous fat tissue.

Microscopic peculiarities stemming from a temperature increase in subcutaneous adipose tissue (sWAT) after applying a radio-frequency (RF) current, must be strongly dependent on the type of sWAT. This effect is connected with different electrical conductivities of pathways inside (triglycerides in adipocytes) and outside (extra-cellular matrix) the cells and to the different weighting of these pathways in hypertrophic and hyperplastic types of sWAT. The application of the RF current to hypertrophic sWAT, which normally has a strongly developed extracellular matrix with high concentrations of hyaluronan and collagen in a peri-cellular space of adipocytes, can produce, micro-structurally, a highly inhomogeneous temperature distribution, characterized by strong temperature gradients between the peri-cellular sheath of the extra-cellular matrix around the hypertrophic adipocytes and their volumes. In addition to normal temperature effects, which are generally considered in body contouring, these temperature gradients can produce thermo-mechanical stresses on the cells' surfaces. Whereas these stresses are relatively small under normal conditions and cannot cause any direct fracturing or damage of the cell structure, these stresses can, under some supportive conditions, be theoretically increased by several orders of magnitude, causing the thermo-mechanical cell damage. This effect cannot be realized in sWAT of normal or hyperplastic types where the peri-cellular structures are under-developed. It is concluded that the results of RF application in body contouring procedures must be strongly dependent on the morphological structure of sWAT

Influence of the Dermis Thickness on the Results of the Skin Treatment with Monopolar and Bipolar Radiofrequency Currents

Electrically layered tissue structure significantly modifies distribution of radiofrequency (RF) current in the dermis and in the subcutaneous adipose tissue comparing to that in a homogeneous medium. On the basis of the simple model of RF current distribution in a two-layer skin containing dermis and subcutis, we assess the influence of the dermal thickness on the current density in different skin layers. Under other equal conditions, current density in the dermis is higher for the skin having thinner dermis. This contradicts the main paradigm of the RF theory stating that treatment results are mainly dependent on the maximal temperature reached in a target tissue, since the best short- and long-term clinical results of RF application to the skin were reported in the areas having thicker dermis. To resolve this contradiction, it is proposed that the long-term effect of RF can be realized through a structural modification of the subcutaneous fat depot adjacent to the treated skin area. Stimulation of these cells located near the interface dermis/subcutis will demand the concentration of applied RF energy in this area and will require the optimal arrangement of RF electrodes on the skin surface

Caveolin-1 as a pathophysiological factor and target in psoriasis

Abstract Low expression of caveolin-1 (Cav-1) is typical in psoriatic lesions and overexpression of Cav-1 leads to a reduction of inflammation and suppression of epidermal hyperproliferation, thus ameliorating these two well-known hallmarks of psoriasis. At the same time, the interfacial layers of the white adipose tissue (WAT) adjacent to psoriatic lesions demonstrate much higher stiffness, which also points to a modification of Cav-1 expression in this tissue. These processes are connected with each other and regulated via exosomal exchange. Here we discuss the role of Cav-1 expression in inflammatory and hyperproliferative processes and analyze the ways to provide spatially different modulation of Cav-1 expression in the skin and WAT. Such modulation can be induced by different pharmacological and physical factors. These include application of mechanical stress and supra-physiological temperatures. Cav-1 should therefore be considered as an important target in treatment of psoriasis