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

Wen-Chao Zhang,Xiao-Jun Wang,Ming-Zi Zhang,Xiao Long,Lin Zhu,Zhi-Fei Liu,Feng Qin,Nan-Ze Yu,Ang Zeng

doi:10.1155/2019/1731540

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.

Highlights

Obesity is a disease accompanied by abnormal fat deposition and is closely associated with endocrine and metabolic dysfunction, inflammation, oxidative stress, and insulin resistance [1]
The results indicated that the significant differentially expressed genes of the differentiated adipocytes engaged in lipid metabolism pathway, Peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway, and insulin resistance pathway
The major biological processes of lipid metabolism and mitochondrial transport were found to be intertwined with the process of Adipose-derived mesenchymal stromal cells (ADSCs) differentiation into adipocytes (Figure 1)

Summary

Introduction

Obesity is a disease accompanied by abnormal fat deposition and is closely associated with endocrine and metabolic dysfunction, inflammation, oxidative stress, and insulin resistance [1]. In the adipose tissues of humans, there are three types of adipocytes, namely, white adipocytes, brown adipocytes, and beige adipocytes. White adipocytes mainly regulate lipid synthesis and storage, whereas both brown adipocytes and beige adipocytes significantly contribute to regulation of energy consumption through activation of uncoupling protein 1 (UCP1) in mitochondria [2, 3]. Both brown and beige adipocytes could produce a set of adipokines to engage in pathways for autocrinal, paracrinal, and metabolic activities [4]. Research on the different functions in metabolism that have important relationships to and can be influenced by brown and beige adipocytes has not been extensively undertaken [7]

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Results

Discussion

Conclusion