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Updated: Mar 23, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Local proliferation initiates macrophage accumulation in adipose tissue during obesity
1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Obesity-associated chronic inflammation is characterized by an accumulation of adipose tissue macrophages (ATMs). It is generally believed that those macrophages are derived from peripheral blood monocytes. However, recent studies suggest that local proliferation of macrophages is responsible for ATM accumulation. In the present study, we revealed that both migration and proliferation contribute to ATM accumulation during obesity development. We show that there is a significant increase in ATMs at the early stage of obesity, which is largely due to an enhanced in situ macrophage proliferation. This result was obtained by employing fat-shielded irradiation and bone marrow reconstitution. Additionally, the production of CCL2, a pivotal chemoattractant of monocytes, was not found to be increased at this stage, corroborating with a critical role of proliferation. Nonetheless, as obesity proceeds, the role of monocyte migration into adipose tissue becomes more significant and those new immigrants further proliferate locally. These proliferating ATMs mainly reside in crown-like structures formed by macrophages surrounding dead adipocytes. We further showed that IL-4/STAT6 is a driving force for ATM proliferation. Therefore, we demonstrated that local proliferation of resident macrophages contributes to ATM accumulation during obesity development and has a key role in obesity-associated inflammation.
Insights
Local macrophage proliferation, not just monocyte migration, drives adipose tissue macrophage accumulation in early obesity. This finding is crucial for understanding obesity-associated inflammation.
Area of Science:
- Immunology
- Metabolic Diseases
- Cell Biology
Background:
- Obesity-associated chronic inflammation involves adipose tissue macrophages (ATMs).
- Traditionally, ATMs were thought to originate solely from peripheral blood monocytes.
- Emerging evidence suggests local macrophage proliferation contributes to ATM accumulation.
Purpose of the Study:
- To investigate the relative contributions of monocyte migration and local proliferation to ATM accumulation during obesity development.
- To elucidate the mechanisms driving ATM accumulation and their role in obesity-associated inflammation.
Main Methods:
- Utilized fat-shielded irradiation and bone marrow reconstitution models in mice.
- Analyzed ATM populations at different stages of obesity.
- Investigated the role of CCL2 and the IL-4/STAT6 signaling pathway.
Main Results:
- ATM accumulation in early obesity is primarily driven by enhanced in situ macrophage proliferation, not monocyte migration.
- CCL2 levels were not significantly increased in early obesity, supporting a proliferation-driven mechanism.
- As obesity progresses, monocyte migration becomes more significant, with these new cells also proliferating locally.
- Proliferating ATMs were observed in crown-like structures around dead adipocytes.
- The IL-4/STAT6 pathway was identified as a key driver of ATM proliferation.
Conclusions:
- Local proliferation of resident macrophages significantly contributes to ATM accumulation in obesity.
- Macrophage proliferation plays a critical role in obesity-associated chronic inflammation.
- Both proliferation and migration of macrophages are important for ATM accumulation, with proliferation dominating early stages.
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