Anti-obesity effect and mechanism of mesenchymal stem cells influence on obese mice
Zongyan Xie1, Yu Cheng2, Qi Zhang3
1Department of Clinical Pharmacology, Beijing Luhe Hospital Affiliated to Capital Medical University, 82 Xinhua South Road, Beijing 101149, People's Republic of China.
Abstract:
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 O2 consumption, CO2 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.
Insights
Human adipose-derived mesenchymal stem cells (hASCs) effectively combat obesity by boosting metabolism and energy expenditure. These stem cells promote M2 macrophage activity, reducing inflammation and improving lipid profiles in obese mice.
Area of Science:
- Stem Cell Therapy
- Metabolic Diseases
- Obesity Research
Background:
- Mesenchymal stem cells (MSCs) show therapeutic potential for metabolic diseases.
- Human adipose-derived MSCs (hASCs) are easily accessible and have low immunogenicity.
- Obesity is a growing metabolic concern requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of hASCs on obesity in high-fat diet-induced obese mice.
- To elucidate the underlying mechanisms of hASCs' anti-obesity effects.
- To analyze changes in macrophage phenotypes and inflammatory markers.
Main Methods:
- Mice were fed a high-fat diet (HFD) for 16 weeks, followed by intravenous hASCs injection.
- Body weight, composition, and energy expenditure were assessed post-treatment.
- Macrophage infiltration in adipose tissue and gene expression (UCP-1, metabolism-associated, pro-inflammatory cytokines) were analyzed.
Main Results:
- hASCs administration significantly reduced adipose tissue weight, adipocyte size, and overall fat mass.
- Treatment improved serum lipid profiles and increased oxygen consumption, carbon dioxide production, and energy expenditure.
- hASCs promoted M2 macrophage polarization in adipose tissue and decreased pro-inflammatory cytokine gene expression.
Conclusions:
- hASCs suppress obesity by upregulating uncoupling protein-1 (UCP-1) and enhancing energy expenditure.
- The anti-obesity effects of hASCs may be mediated by increased M2 macrophages in adipose tissue.
- hASCs represent a promising therapeutic approach for managing obesity and related metabolic disorders.
