Xie Zongyan, Cheng Yu, Zhang Qi, Hao Haojie, Yin Yaqi, Zang Li, Wang Xuhong, Mu Yiming
Department of Clinical Pharmacology, Beijing Luhe Hospital Affiliated to Capital Medical University, 82 Xinhua South Road, Beijing 101149, People's Republic of China.
Department of Endocrinology, The First Medical Center of PLA General Hospital, 28 Fuxing Road, Beijing 100853, People's Republic of China.
Open Life Sci. 2021 Jun 25;16(1):653-666. doi: 10.1515/biol-2021-0061. eCollection 2021.
Mesenchymal stem cells (MSCs) can be obtained from almost all tissues and present promising therapeutic effects for metabolic diseases. Human adipose-derived MSCs (hASCs) have recently been widely studied due to their easy access and low immunity. Thus, we intended to figure out the effects and potential mechanism of hASCs on obesity in high-fat-diet (HFD)-induced obese mice. Following 16 weeks of being fed HFD, hASCs were intravenously injected. Two weeks later, body weight, body composition, and energy expenditure were evaluated. Additionally, the phenotypes of macrophages infiltrating adipose tissue were analyzed. The results revealed that hASCs administration significantly reduced adipose tissue weight, adipocyte size, and fat mass and exerted beneficial effects in serum lipid profile. This anti-obesity effect was mediated by the increased O consumption, CO production, and energy expenditure, which was further evidenced by the upregulation of uncoupling protein-1 (UCP-1) and metabolism-associated genes. Furthermore, hASCs infusion increased the amount of alternatively activated (M2) macrophages in adipose tissue, and the expression of pro-inflammatory cytokines-related genes was reduced. Taken together, these results indicated that hASCs suppressed obesity by increasing UCP-1 expression and enhancing energy expenditure, and this effect might be due to the increased M2 macrophages.
间充质干细胞(MSCs)几乎可从所有组织中获取,对代谢性疾病具有潜在的治疗作用。人脂肪来源的间充质干细胞(hASCs)因其易于获取和低免疫原性,近年来受到广泛研究。因此,我们旨在探究hASCs对高脂饮食(HFD)诱导的肥胖小鼠肥胖的影响及其潜在机制。在给予HFD喂养16周后,静脉注射hASCs。两周后,评估体重、身体成分和能量消耗。此外,分析了浸润脂肪组织的巨噬细胞表型。结果显示,给予hASCs显著降低了脂肪组织重量、脂肪细胞大小和脂肪量,并对血脂谱产生有益影响。这种抗肥胖作用是由耗氧量增加、二氧化碳产生和能量消耗介导的,解偶联蛋白-1(UCP-1)和代谢相关基因的上调进一步证明了这一点。此外,输注hASCs增加了脂肪组织中交替活化(M2)巨噬细胞的数量,并降低了促炎细胞因子相关基因的表达。综上所述,这些结果表明,hASCs通过增加UCP-1表达和增强能量消耗来抑制肥胖,这种作用可能归因于M2巨噬细胞的增加。