Molecular and Physiological Effects of Browning Agents on White Adipocytes from Bone Marrow Mesenchymal Stromal Cells

Abstract

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the ‘browning of WAT’. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity.

Irisin influences the in vitro differentiation of human mesenchymal stromal cells, promoting a tendency toward beiging adipogenesis

“…MSCs (passage 3-4) were expanded according to the manufacturer's recommendation and incubated for 7 days with 20 nM of Irisin, we already demonstrated was effective in previous findings. 26 Specifically, we examined its impact on important biological parameters including cell survival, senescence, apoptosis, and DNA damage. By assessing these key parameters, we aimed to gain insights into the potential cellular responses to Irisin treatment and its influence on cellular viability, aging processes, programmed cell death, and DNA integrity.…”

“…Indeed, in a previous research we demonstrated the ability of Irisin to promote beiging of white adipocytes obtained from terminally differentiated cells. 26 However, it is essential for a safe and efficacious antiobesity medication to have minimal impact on the functionality of other cell types, especially stem cells, as they serve as a vital reservoir within the organism for maintaining tissue balance and homeostasis. When a drug reaches the WAT depots, its effects extend beyond mature adipocytes and impact various other cell types present within this tissue, such as MSCs.…”

“…10,25 In our previous study, we assessed the potential of browning drugs, such as Irisin, to induce the browning process in adult mature adipocytes derived from terminally differentiated mesenchymal stromal cells (MSCs). 26 In the current research, we investigated the effects of Irisin as browning myokine on MSCs, which have the ability to differentiate into both brown and white adipocytes. 21,22 MSCs are found within WAT depots.…”

Mechanisms of Transmission and Processing of Pain: A Narrative Review

“…Nociceptors may also be sensitized by T cells that release IL-17A and IFN-γ, which act at nerve terminals to increase neuropathic pain [ 113 ]. It has been shown, in recent years, that mesenchymal stromal cells (MSCs), which have the ability to differentiate into distinct mesenchymal cell lineages, including chondrogenic, adipogenic, and osteogenic lineages, [ 114 , 115 ], are able to modulate the inflammatory response through interleukin-10 (IL-10). During inflammation, different regulatory immune cells are induced, and their population is expanded.…”

“…Furthermore, TRPV1 currents in DRG are inhibited by maresin 1, which reduces inflammatory pain [ 143 ]. Neither protectin D1 nor maresin 1 influence nociceptive mechanisms downstream of TRPA1 [ 115 , 145 ]. These results, when considered together, may open a new viewpoint towards the role of pro-inflammatory lipids, such as PGE2 and LTB4, in the activation of pain.…”