Molecular medicine-Adipose Dysfunction and Metabolic Disease

Just as our appreciation of how active a role
the adipose tissue plays in the metabolic
regulation has grown in recent years, so too
has the interest in the role that adipocytes
play in the development (and treatment)
of metabolic diseases such as obesity and
diabetes. The investigation of the role
of adipose tissue in these diseases has
taken on addedsignificance inrecent years
14 Adipocytes
because of the dramatic rise in the prevalence
of these related disorders. Although
the causal relationship between diabetes
and obesity is not fully understood, a likely
common link is the adipocyte. Given that
adipose tissue serves to buffer excess lipid,
and to confer insulin resistance that is associated
with inappropriate accumulation
of lipid in nonadipose cells, it is not surprising
that the dysfunction in adipose
tissue could profoundly affect diabetes susceptibility.
The inability of adipose tissue
to buffer circulating lipid levels and concurrent
accumulation of lipid in muscle
and liver may, in fact, be an early event in
the development of diabetes. This potential
link between adipose tissue function
and diabetes raises the new and exciting
possibilities for the development of
therapeutic agents to treat diabetes. Drugs
targeted to very specific metabolic or hormonal
functions in the adipocyte could
potentially have a profound beneficial effects
on metabolism throughout the body.
The following is a summary of the known
defects in adipose function and their effects
on energy metabolism and glucose
homeostasis. We will also review what is
known about the antidiabetic thiazolidinedione
drugs that are thought to have their
effects by modifying adipocyte physiology.