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Updated: Mar 14, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+
Mariana Renovato-Martins1, Maria Eline Matheus2, Isadora Ramos de Andrade1
1Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Abstract:
Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+ monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+ enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16- monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+ monocytes, favoring leukocyte infiltration in the obese omental AT.
Insights
Obese adipose tissue releases factors that increase CD16+ monocytes, enhancing their migration and contributing to inflammation. This creates a feedback loop promoting leukocyte infiltration in obesity.
Area of Science:
- Immunology
- Metabolic disorders
- Cell biology
Background:
- Macrophage infiltration into adipose tissue (AT) is characteristic of obesity-related chronic inflammation.
- Increased CD16+ monocyte subsets are observed in obesity, but underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate if factors secreted by obese omental AT polarize monocytes to a CD16+ phenotype.
- To determine how these changes affect monocyte migration towards AT.
Main Methods:
- Explants of human obese omental AT and lean subcutaneous AT were used.
- Monocytes were exposed to conditioned media and microparticles (MP) from AT.
- Expression of CD16, CCR5, and TLR8 was analyzed.
- Monocyte migration assays were performed.
- MIP1-α neutralization and MP transfer experiments were conducted.
Main Results:
- Obese omental AT released higher levels of MIP1-α, TNFα, leptin, VEGF, and MP compared to lean AT.
- Circulating MP from preadipocytes and leukocytes were elevated in obese subjects.
- Obese AT-derived conditioned media and MP increased CD16 and CCR5 on monocytes, enhancing their migration.
- This effect was mediated by MIP1-α and TLR8 transfer via MP.
- A positive feedback loop between blood monocytes and obese AT was identified.
Conclusions:
- Obese omental AT actively promotes CD16+ monocyte polarization and migration through secreted factors and MP.
- TLR8 transfer by MP from obese AT upregulates CD16 on monocytes.
- This establishes a feedback loop exacerbating inflammation and leukocyte infiltration in obese adipose tissue.
