Adipocytes
3
and organs throughout the body. This new view of adipose tissue (and the adipocyte)
as a key regulator of fuel metabolism and partitioning has dramatically increased
the interest in the role that this tissue plays not only in normal physiology but also
in the etiology and treatment of important metabolic diseases such as diabetes and
obesity.
1
Introduction – Adipocytes and the
Regulation of Metabolism
Although the physiology of adipose tissue
and the molecular and cellular biology of
the adipocyte have been subjects of re-
search interest for many years, new work
in this area has transformed our under-
standing of the adipocyte and its role in
regulating human physiology. We now
recognize that in addition to its long appre-
ciated function as a lipid storage depot, the
adipocyte plays a much more active role
in regulating whole body fuel partitioning
and metabolism. The growing interest in
the physiology of adipose tissue and the
role that it plays in metabolic regulation is
fueled to a large degree by the realization
that we are in the midst of a growing
epidemic of the metabolic disorders of
diabetes and obesity. In most developed
countries, the incidence of both of these
diseases has increased dramatically in the
past few decades. Currently (as of 2003),
there are 16 million diabetics in the United
States, and the incidence of the disease has
increased by 49% from 1990 to 2000, with
projections indicating a 165% increase by
2050. There has also been a dramatic in-
crease in the incidence of obesity, with over
one-third of the population in the United
States now classiFed as obese. Although
the causal relationship between diabetes
and obesity is not fully understood, a likely
common link is the adipocyte.
In healthy individuals, excess fat is
stored
in
adipocytes
while
only
low
amounts of triglyceride are maintained in
nonadipocytes. It is thought that in obese
individuals, the capacity for adipose tissue
to accommodate excess lipid is exceeded,
resulting in the abnormal accumulation
of lipid in other tissues. This elevation in
intracellular triglyceride content has been
associated with physiological dysfunction
(lipotoxicity) that contributes to the devel-
opment of obesity-related type 2 diabetes.
This pathological accumulation of lipid in
nonadipose tissue may be the result of a
physiological dysfunction of the adipocyte
that is induced by the obese state. In this
chapter, we will review the current state of
knowledge about fat cell lipid metabolism,
and how adipocytes function to balance
lipid storage and mobilization to meet
the energetic demands of the organism
without exposing nonadipose tissues to
deleterious fat accumulation.
In addition to its function as an energy-
storage depot, we now understand that
adipose tissue is also a bona Fde en-
docrine organ, secreting hormones that
regulate fat metabolism in other tissues
throughout the body. The list of biologi-
cally active peptides known to be secreted
by fat cells has grown signiFcantly in re-
cent years, and although the physiological
function of most of these adipocyte-derived
hormones (adipokines) is not fully under-
stood, it is clear that they are important
components of the physiological system
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