Adipose-Derived Stromal Cells Attenuate Adipose Inflammation in Obesity through Adipocyte Browning and Polarization of M2 Macrophages

Abstract

Obesity is a metabolic condition associated with multiple health problems such as endocrine and metabolic dysfunction and chronic inflammation in adipose tissues. In this study, the ADSCs could be stimulated to differentiate into brown adipocyte with rosiglitazone treatment based on the Oil-Red-O staining trial. Furthermore, the multilocular lipid droplets located in the center was increased in differentiated brown adipocytes, and brown fat-associated proteins, UCP1, PPAR-γ, and LPL were highly expressed in brown adipocytes differentiated from ADSCs. Additionally, the results of animal experiments showed that both weight and amount of VLDL and LDL were decreased in the serum of obese mice after transplantation of rosiglitazone-induced brown adipocytes, while the level of HDL increased. Moreover, the proteins associated with lipid metabolism, LPA and UCP1, were downregulated, and the inflammatory response was suppressed through inhibition of the ITGAM/NF-κB-mediated proinflammatory responses and polarization of M2 macrophages. Similarly, the amounts of proinflammatory cytokines, TNF-α, IL-6, and IL-1β were decreased after rosiglitazone-induced brown adipocyte transplantation. On the contrary, anti-inflammatory cytokine IL-10 was significantly increased in both groups of obese mice, with or without brown adipocyte transplantation. Therefore, the adipose-derived stromal cells with induced browning could promote lipid consumption and alternative polarization of M2 macrophages to attenuate adipose inflammation in obesity mouse models, which thus provides a potential therapy for obesity.

Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

“…It had already been shown that proinflammatory M1 macrophages infiltrating BAT impair its ability to appropriately respond to thermogenic stimuli, by the secretion of TNFα and IL‐1β that suppress the induction of Ucp1 gene expression [48,49]. Since Mcpip1 inhibits the classic activation of M1 macrophages and promotes M2 polarization, we postulate that the hypothermia of Mcpip1 fl/fl LysM Cre mice might be at least partially explained by an increased infiltration of M1 macrophages into BAT and a high level of Tnfa [29,50].…”

Use of brown adipose tissue transplantation and engineering as a thermogenic therapy in obesity and metabolic disease

“…This reduced body mass and serum levels of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol and increased high density lipoprotein (HDL) cholesterol levels in recipients. 54 However, some studies have indicated the limitations of such strategies in clinical applications. 18,55 Primary concern is that the period of ASC proliferation and differentiation potential in vivo is short and negatively correlated with age.…”

“…Specifically, transplanted mice show increased oxygen consumption, respiratory rate, and overall energy consumption. 54 For all these important findings, there are still a number of hurdles associated with iPSC-based therapy that will need to be overcome.…”

Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

“…The immunomodulatory effects of MSCs have been observed in obesity. As described by Zhang et al., adipose-derived stem cells (ADSCs) suppress pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the obese mice through inhibition of the ITGAM/NF-κB pathway and polarisation of M2 macrophages [ 154 ]. Another recent study found that lean mouse-derived ADSCs treatment successfully reduced obesity-associated white adipose tissue inflammation and substantially improved insulin action in obese mice by re-modulating the phenotypes of adipose-resident macrophages from pro-inflammatory M1 toward anti-inflammatory M2 subtypes [ 155 ].…”