Adipocytes
9
and insulin resistance promoting activity
of these adipokines raises the possibility
that it contributes to the functional link
between obesity and diabetes. Although a
great deal more work needs to be done in
this area before we can fully appreciate the
multiple roles that adipokine hormones
play in the regulation of metabolism, it
is clear that they are a crucial component
of the physiological system that regulates
energy balance and fuel partitioning.
3
Developmental Origin of Adipocytes
3.1
Adipose Tissue Development and Plasticity
The basic functional unit of adipose tis-
sue is the adipocyte. Nevertheless, adipose
tissue is complex and contains several
cell types in addition to adipocytes, such
as endothelial cells, interstitial cells, un-
differentiated mesenchymal cells, peri-
cytes, and ‘‘very small adipocytes’’. Indeed,
adipocytes constitute less than 20% of the
cells residing in typical adult fat tissue.
Moreover, there are very important inter-
actions among the various cell types that
are critical to the proper functioning of
the tissue. In view of the huge increase
in obesity rates in the United States, and
its negative impact on health, new atten-
tion has been focused on the development,
maintenance, and plasticity of this impor-
tant tissue.
Analysis of adipose tissue histogenesis
and remodeling has relied mainly upon
descriptive approaches to deFne cell phe-
notypes and deduce their transition to
mature cells. In humans, adipose tissue ap-
pearsasdistinctlobulesduringthesecond
trimester of fetal development. The spe-
ciFc timing of adipose tissue histogenesis
and fat cell differentiation varies according
to location in the body. Adipocytes within
f
a
tt
i
s
su
ea
r
ethough
ttod
e
r
i
v
ein
i
t
i
a
l
l
y
from mesenchymal progenitors capable
of differentiating into bone, muscle, as
well as fat. Mesenchymal cells that are
highly committed to the adipocyte lineage
Frst appear closely associated with ves-
sel formation, and there appears to be a
close reciprocal association of developing
fat cells with angiogenesis. This is not
surprising since early committed cells ex-
press lipoprotein lipase that is targeted
at the capillary lumen, and provides the
mechanism for the transport of dietary
triglyceride to Fll the developing fat cells.
As fat cells develop, triglycerides coalesce
into small lipid droplets (nearly all of which
are triglycerides) within the cytoplasm that
eventually fuse to form a large single lipid
droplet. The typical mature adipocyte is rel-
atively large (30–50 micron diameter) and
can reach a size of greater than 120
µ
m
under certain conditions (±ig. 2).
Experimental investigations of adipose
tissue have mainly utilized rodent models,
although it is important to note that the
ontogeny of adipose tissue varies widely
among species, and even among fat depots
within a given species. In rodent models,
white adipose tissue generally appears late
in embryonic development and continues
to expand and differentiate during the
neonatal period prior to weaning. Classic
‘‘flash’’
labeling
experiments with
an
3
H thymidine have shown that most
proliferation of cells that are destined
to become adipocytes occurs in the Frst
postnatal week. Mitoses are mostly found
in poorly differentiated mesenchymal cells
that are closely associated with developing
capillaries. The transition of cells from
mesenchymal progenitors to mature cells
can be deduced by evaluating the cellular
distribution of
3
H label over time following
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