Control (14 days)
TZD (14 days)
Fig. 4
Thiazolidinedione treatment remodels
white adipose tissue. Mice were treated for
2 weeks with the TZD T174, and subcutaneous
white fat was processed by (a) hematoxylin and
eosin staining and (b) tissue autofluorescence.
Note the appearance of numerous clusters of
small multilocular adipocytes in TZD-treated
appearing small adipocytes might be more
insulin sensitive and/or secrete lower lev-
els of prodiabetes hormones and thereby
contribute to the insulin-sensitizing effects
of the drug. It is also possible that the
increased number of smaller adipocytes,
especially in the appropriate adipose beds,
may improve the ability of adipose tissue
to store excess lipid and reduce deleterious
accumulation of triglyceride in muscle,
liver, and pancreatic islets. In support of
this possibility is the observation that many
of the known target genes for PPAR
whose expression would presumably be ac-
tivated upon TZD treatment, are involved
in lipogenesis. The increased rates of
lipogenesis resulting from gene activation
may increase the capacity of adipocytes to
store lipid, thereby preventing triglyceride
accumulation (and lipotoxicity) in nonadi-
pose tissue. Whether the small adipocytes
are derived from stem cell mitosis, re-
cruitment of committed preadipocytes, or
possibly by division of mature cells is not
known. The loss of large fat cells was at-
tributed to cellular apoptosis; however, the
impact of TZD treatment on the fate and
turnover of mature adipocytes has not been
investigated directly.
Consistent with the observations of adi-
pose tissue remodeling is the increased
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