Mathematical Models of Adipose Tissue Dynamics - The Mechanobiology of Obesity and Related Diseases - page 16

4.1 Recruitment of New Adipose Cells

An old hypothesis is that the total number of adipose cells does not increase after a
critical developmental period. Although this is partly true for some fat depots such
as epididymal fat [ 4 ], the hypothesis has been revised due to experimental evi-
dence that new adipose cells can be recruited in adults not only under stimulating
conditions such as lipectomy [ 4 ] and high-fat diet [ 5 ], but also under normal
conditions [ 3 ]. Spalding et al. [ 3 ] have reported that human adipose cells turn over
with a period of 10 years, although total cell number is fixed. However, the
sources of new adipose cells are still controversial. Pre-existing preadipocytes and
stem cells in adipose tissues are potential candidates [ 22 ], because mature adipose
cells are known to be post-mitotic cells incapable of proliferation [ 23 ]. Under
weight gain conditions, we have confirmed that small adipose cells (\25 l m
diameter) are recruited based on the evolution of adipose cell-size distribution
under high-fat diet [ 16 ]. Furthermore, the recruitment rate strongly depends on
genetics as well as diet.

4.2 Size-Dependent Growth/Shrinkage

The growth and shrinkage of adipose cells are basically governed by the bio-
chemical processes of lipogenesis and lipolysis, respectively. Therefore, the
growth/shrinkage rate depending on adipose cell size s can be described by two
terms:

v ð s Þ ¼v þ ð s Þ v ð s Þ: ð 12 Þ

As a simple size dependency, we may assume that both lipogenesis and
lipolysis in adipose cells are biochemical processes limited by cell-surface area, if
adipose cells are sufficiently mature (i.e., larger than a certain critical size). Note
that the critical cell size for the two processes may not be the same in general. This
assumption suggests a simple size-dependent growth/shrinkage rate of adipose
cells:

1 þ tanh s s þ
g þ

v m
2

1 þ tanh s s
g

v ð s Þ ¼ v þ
2

ð 13 Þ

where v m represents the maximal lipogenesis/lipolysis rate; s is the critical size
for lipogenesis/lipolysis, which gives the half-maximal growth/shrinkage rate; and
g gives their steepness [ 24 ]. We confirmed that the function v ð s Þ satisfactorily
explains the evolution of adipose cell-size distribution under positive and negative
energy balance, and inferred corresponding likelihood values of these parameters
[ 17 ]. For example, the maximal lipogenesis rate v þ has a larger value under high-
fat diet, compared with the value under regular diet, that allows the accelerated