Abstract
In the treatment of obesity and its related disorders, one of the measures adopted is weight reduction by controlling nutrition and increasing physical activity. A valid alternative to restore the physiological function of the human body could be the increase of energy consumption by inducing the browning of adipose tissue. To this purpose, we tested the ability of Histogel, a natural mixture of glycosaminoglycans isolated from animal Wharton jelly, to sustain the differentiation of adipose derived mesenchymal cells (ADSCs) into brown-like cells expressing UCP-1. Differentiated cells show a higher energy metabolism compared to undifferentiated mesenchymal cells. Furthermore, Histogel acts as a pro-angiogenic matrix, induces endothelial cell proliferation and sprouting in a three-dimensional gel in vitro, and stimulates neovascularization when applied in vivo on top of the chicken embryo chorioallantoic membrane or injected subcutaneously in mice. In addition to the pro-angiogenic activity of Histogel, also the ADSC derived beige cells contribute to activating endothelial cells. These data led us to propose Histogel as a promising scaffold for the modulation of the thermogenic behavior of adipose tissue. Indeed, Histogel simultaneously supports the acquisition of brown tissue markers and activates the vasculature process necessary for the correct function of the thermogenic tissue. Thus, Histogel represents a valid candidate for the development of bioscaffolds to increase the amount of brown adipose tissue in patients with metabolic disorders.
Highlights
Obesity represents a major health problem associated with increased mortality and co-morbidities, including many metabolic diseases [1]
Histogel is a natural mixture of glycosaminoglycans including, among others, high grade hyaluronic acid (HA) and chondroitin sulfate obtained from the Wharton jelly found in umbilical cords of animal origin [20]
Since hyaluronan is a mix of molecules with different masses and the molecular weight confers different biological properties to hyaluronan preparations, a first set of experiments was performed to compare the amount and the molecular weight of hyaluronan contained in different Histogel preparations
Summary
Obesity represents a major health problem associated with increased mortality and co-morbidities, including many metabolic diseases [1]. Obesity is characterized by an increase in adipose mass due to increased energy intake, decreased energy expenditure, or both. Environmental, neuro-psychological, genetic, and epigenetic factors contribute to increase the energy intake (calories) and to reduce the energy expenditure (metabolic and physical activity). Cells 2019, 8, 1457 options for patients with severe obesity are the modification of lifestyle, limiting the intake of total fats and sugars, increasing consumption of fruits, vegetables, and whole grains and practicing regular physical activity or pharmacological treatments currently available in the market, which are commonly associated with severe side effects. The increase of energy consumption through the increase of metabolism and thermogenesis of the adipose tissue may be a valid alternative [6]
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