Molecular medicine-The Adipocyte as a Therapeutic Target for Metabolic Disease

The Adipocyte as a Therapeutic Target for
Metabolic Disease
As our understanding of the importance
of adipose tissue in controlling
metabolism has grown, so too has the realization
that therapeutic agents designed
to modify adipocyte physiology could provide
new avenues for the treatment of
diabetes, obesity, and other metabolic
16 Adipocytes
diseases. As described above, our current
understanding of the role of adipose
in protecting other tissue from deleterious
lipid accumulation suggests that
drugs acting on this aspect of adipocyte
function might have beneficial effects.
Likewise, the observations (also described
above) on adipocyte derived hormones and
their metabolic activities, suggests that
therapeutic agentsmodulating the production
of key adipokines could also improve
certain metabolic parameters. The view
that drugs acting on adipocytes could be
useful is reinforced by the relatively recent
observation that a major class of antidiabetic
drugs, the thiazolidinediones, have
direct effects on adipocytes. Although this
is an active area of research, a generally accepted
model of TZD action has emerged
in which the antidiabetic effect of these
drugs is mediated by activation of the
PPARγ transcription factor in adipocytes.
The following is a review of our current understanding
of how activation of PPARγ
in adipocytes might improve insulin sensitivity
and other metabolic parameters.
This model can serve as a general example
of how modification of adipocyte physiology
could improve whole body metabolic
status.