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Updated: Aug 16, 2026
Adipo-Clear: A Tissue Clearing Method for Three-Dimensional Imaging of Adipose Tissue
Published on: July 28, 2018
Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans
Saverio Cinti1, Grant Mitchell, Giorgio Barbatelli
1Institute of Normal Human Morphology, University of Ancona, Ancona, Italy.
Abstract:
Macrophage infiltration of white adipose tissue (WAT) is implicated in the metabolic complications of obesity. The precipitating event(s) and function(s) of macrophage infiltration into WAT are unknown. We demonstrate that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where they fuse to form syncytia that sequester and scavenge the residual "free" adipocyte lipid droplet and ultimately form multinucleate giant cells, a hallmark of chronic inflammation. Adipocyte death increases in obese (db/db) mice (30-fold) and humans and exhibits ultrastructural features of necrosis (but not apoptosis). These observations identify necrotic-like adipocyte death as a pathologic hallmark of obesity and suggest that scavenging of adipocyte debris is an important function of WAT macrophages in obese individuals. The frequency of adipocyte death is positively correlated with increased adipocyte size in obese mice and humans and in hormone-sensitive lipase-deficient (HSL-/-) mice, a model of adipocyte hypertrophy without increased adipose mass. WAT of HSL-/- mice exhibited a 15-fold increase in necrotic-like adipocyte death and formation of macrophage syncytia, coincident with increased tumor necrosis factor-alpha gene expression. These results provide a novel framework for understanding macrophage recruitment, function, and persistence in WAT of obese individuals.
Insights
Obesity causes white adipose tissue (WAT) macrophages to cluster around dead fat cells, forming inflammatory giant cells. This necrotic-like adipocyte death is a key feature of obesity, with macrophages clearing cellular debris.
Area of Science:
- Cell Biology
- Immunology
- Metabolic Disease Research
Background:
- Macrophage infiltration into white adipose tissue (WAT) is linked to obesity's metabolic issues.
- The triggers and roles of macrophages in WAT during obesity remain unclear.
Purpose of the Study:
- To investigate the localization and function of macrophages within WAT in obesity.
- To identify the nature of adipocyte death and its relationship with macrophage activity in obese states.
Main Methods:
- Analysis of WAT macrophages in obese mice (db/db, HSL-/-) and humans.
- Microscopic examination of adipocyte death ultrastructure.
- Correlation analysis between adipocyte size, death frequency, and macrophage presence.
Main Results:
- Over 90% of WAT macrophages in obese subjects are found near dead adipocytes, forming syncytia and giant cells.
- Adipocyte death in obesity exhibits necrotic-like features, increasing significantly (30-fold in mice, elevated in humans).
- Adipocyte death frequency correlates positively with adipocyte size and is increased in HSL-/- mice, accompanied by TNF-α expression.
Conclusions:
- Necrotic-like adipocyte death is a pathological hallmark of obesity.
- WAT macrophages primarily function to scavenge adipocyte debris in obese individuals.
- These findings offer a new perspective on macrophage dynamics in obese WAT.
