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Updated: Apr 10, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Inflamed macrophage microvesicles induce insulin resistance in human adipocytes
Yaqin Zhang1,2, Li Shi1,2, Hongliang Mei2
1The Affiliated Drum Tower Hospital of Nanjing Medical University, Nanjing, Jiangsu 21008 China.
Background:
Cytokines secreted by adipose tissue macrophages (ATMs) significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. However, little relevant information is available regarding the role of microvesicles (MVs) derived from ATMs in macrophage-adipocyte crosstalk.
Methods:
MVs were generated by stimulation of M1 or M2 phenotype THP-1 macrophages and incubated with human primary mature adipocytes and differentiated adipocytes. Subsequently, insulin-stimulated phosphorylation of Akt (pAkt) and glucose uptake were determined. Glucose transporter 4 (GLUT4) translocation and nuclear translocation of nuclear factor (NF)-kappa B were also analyzed in treated adipocytes.
Results:
M1 macrophage-derived MVs (M1 MVs) significantly reduced protein abundance of insulin-induced Akt phosphorylation in human primary mature adipocytes and differentiated adipocytes, when compared with the same concentration of M2 macrophage-derived MVs (M2 MVs). In contrast to M2 MVs, which enhanced the insulin-induced glucose uptake measured by 2-NBDG, M1 MVs decreased this effect in treated adipocytes. M1 MVs treatment also brought about a significant increase in the nuclear translocation of nuclear factor (NF)-kappa B, coupled with a decrease in pAkt level and GLUT4 translocation compared with M2 MVs-treated adipocytes. These effects were reversed by BAY 11-7085, a NF- kappa B specific inhibitor.
Conclusions:
MVs derived from proinflammatory (M1) macrophages may, at least in part, contribute to the pathogenesis of obesity-induced insulin resistance, reducing insulin signal transduction and decreasing glucose uptake in human adipocytes, through NF-kappa B activation. Therefore, these MVs may be potential therapy candidates for the management of type 2 diabetes mellitus.
Insights
Microvesicles from M1 macrophages impair insulin sensitivity and glucose uptake in adipocytes by activating NF-kappa B. These microvesicles may be therapeutic targets for type 2 diabetes.
Area of Science:
- Cell Biology
- Metabolic Disease Research
- Immunology
Background:
- Adipose tissue macrophages (ATMs) secrete cytokines that negatively impact adipocyte function, leading to inflammation and reduced insulin sensitivity.
- The role of microvesicles (MVs) from ATMs in macrophage-adipocyte communication remains largely unexplored.
Purpose of the Study:
- To investigate the effect of MVs derived from M1 and M2 macrophages on adipocyte function.
- To elucidate the underlying mechanisms of macrophage-derived MV influence on insulin signaling and glucose uptake.
Main Methods:
- THP-1 macrophages (M1 or M2 phenotype) were stimulated to produce MVs.
- Human primary mature and differentiated adipocytes were incubated with MVs.
- Insulin-stimulated Akt phosphorylation (pAkt), glucose uptake, GLUT4 translocation, and NF-kappa B nuclear translocation were analyzed.
Main Results:
- M1 macrophage-derived MVs (M1 MVs) significantly reduced insulin-induced Akt phosphorylation and glucose uptake in adipocytes compared to M2 MVs.
- M1 MVs increased NF-kappa B nuclear translocation while decreasing pAkt levels and GLUT4 translocation.
- These effects were reversed by the NF-kappa B inhibitor, BAY 11-7085.
Conclusions:
- MVs from proinflammatory M1 macrophages contribute to obesity-induced insulin resistance by impairing insulin signal transduction and glucose uptake in adipocytes via NF-kappa B activation.
- These MVs represent potential therapeutic candidates for managing type 2 diabetes mellitus.
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