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Updated: Sep 11, 2025

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Obesity-associated macrophages dictate adipose stem cell ferroptosis and visceral fat dysfunction by propagating
Yan Tao1, Jinhao Zang1, Tianci Wang1
1Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Abstract:
Morbid obesity induces adipose stem cell (ASC) shortage that impairs visceral adipose tissue (VAT) homeostasis. Macrophages cooperate with ASCs to regulate VAT metabolism, their impact on ASC shortage remains elusive. TNF-α-induced protein 8-like 2 (TIPE2) is an important regulator in immune cells, its expression in VAT macrophages and function in macrophage-ASC crosstalk are largely unknown. Here, TIPE2 loss in VAT macrophages promotes ASC ferroptosis to aggravate diet-induced obesity and metabolic disorders in male mice, which can be corrected by macrophage-specific TIPE2 restoration in VAT. Mechanistically, TIPE2-deficient macrophages propagate mitochondrial fragmentation and reduce delivery of exosomal ferritin toward ASCs, resulting in mitochondrial ROS and Fe2+ overload that dictates ASC ferroptosis. TIPE2 interacts with IP3R to constrain IP3R-Ca2+-Drp1 axis, thereby preventing excessive mitochondrial fission and enabling macrophages to protect against ASC ferroptosis. This study reveals distinct obesity-associated macrophages that dictate ASC ferroptosis, and proposes macrophage TIPE2 as therapeutic target for obesity-related diseases.
Insights
Loss of TIPE2 in macrophages worsens obesity by promoting adipose stem cell ferroptosis. Restoring TIPE2 in macrophages protects against metabolic disorders by preventing cell death.
Area of Science:
- Immunology
- Metabolic Diseases
- Cell Biology
Background:
- Morbid obesity leads to adipose stem cell (ASC) shortage, disrupting visceral adipose tissue (VAT) homeostasis.
- The role of macrophages and TNF-α-induced protein 8-like 2 (TIPE2) in VAT macrophage-ASC crosstalk and ASC shortage is unclear.
Purpose of the Study:
- To investigate the function of TIPE2 in VAT macrophages and its role in macrophage-ASC crosstalk.
- To explore the potential of targeting macrophage TIPE2 as a therapeutic strategy for obesity-related diseases.
Main Methods:
- Utilized male mice models with diet-induced obesity.
- Manipulated TIPE2 expression in VAT macrophages.
- Analyzed ASC ferroptosis, mitochondrial function, and intercellular communication via exosomes.
Main Results:
- TIPE2 deficiency in VAT macrophages promoted ASC ferroptosis, exacerbating obesity and metabolic disorders.
- Macrophage-specific TIPE2 restoration corrected these metabolic impairments.
- TIPE2-deficient macrophages induced mitochondrial fragmentation and reduced exosomal ferritin, leading to ROS and Fe2+ overload in ASCs, causing ferroptosis.
Conclusions:
- Macrophage TIPE2 restrains the IP3R-Ca2+-Drp1 axis, preventing excessive mitochondrial fission and protecting ASCs from ferroptosis.
- Distinct obesity-associated macrophages dictate ASC ferroptosis.
- Macrophage TIPE2 represents a potential therapeutic target for obesity and associated metabolic diseases.
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