Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans
- Publication date
- Publisher
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-a gene expression. These
results provide a novel framework for understanding macrophage
recruitment, function, and persistence in WAT of
obese individuals