Mathematical Models of Adipose Tissue Dynamics - The Mechanobiology of Obesity and Related Diseases - page 17

growth of adipose cells for storing excess lipid. Furthermore, insulin-sensitizing
drugs, thiazolidinediones (TZD), increase the growth rate of adipose cells [ 25 ].
Under conditions of large energy imbalance, one process among lipogenesis
and lipolysis dominates, and the growth/shrinkage rate v ð s Þ is approximated by
either v þ ð s Þ or v ð s Þ . Therefore, the special condition implies that the growth/
shrinkage rate becomes dependent on cell-surface area. The surface-limiting
growth/shrinkage means that larger adipose cells become less efficient for storing
and releasing lipids. This conclusion based on microscopic phenomena could shed
light on the metabolic disorders in obesity where a large number of large adipose
cells are working inefficiently.
4.3 Size Fluctuations and Lipid Turnover
Lipids in adipose cells are continually removed by lipolysis and are replaced by
newly absorbed lipids in a process called lipid turnover [ 26 ]. This turnover can
contribute to size fluctuations of adipose cells. Under continuous high-fat diet, the
bump in the bimodal adipose cell-size distribution becomes flatter (Fig. 2 ). Based
on the fact that stochastic fluctuations are usually involved in the spread of
Gaussian distributions, we added a diffusion term simulating the effects of size
fluctuation of adipose cells on the distribution of adipose cell sizes in the model.
The physical origin of the size fluctuation is the stochastic movement of lipids
across the cell membrane. It turns out that size fluctuations do not contribute much
to the spreading of the distribution as they are dominated by the growth factor v ð s Þ .
However, we found an active potentiating role for size fluctuations for adipose
tissue dynamics. The bimodal size distribution can be divided into a lower peak
and a Gaussian bump. The critical cell size at the nadir of the bimodal distribution
approximately corresponds to the critical cell size for lipogenesis. Therefore, small
cells below the critical size are not capable of growing with the growth process
v ð s Þ . Nevertheless, the size fluctuation of the small cells can sometimes jump them
across the critical cell size. In particular, under high-fat diet, the size fluctuations
increase in magnitude. The larger stochastic jumps allow the transition of more
small cells into mature cells which are capable of growing. These cells progress to
larger sizes and add to the Gaussian bump observed in the adipose cell-size
distribution [ 16 ].
4.4 Cell Death
It has been frequently reported that larger cells are more susceptible to damage
by reactive oxygen species (ROS), hypoxia, and inflammation associated with
infiltration of the adipose tissue by immune cells such as macrophages [ 6 - 8 , 27 ].