Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
It is becoming evident that insulin resistance of white adipose
tissue is a major factor underlying the cardiovascular risk
of obesity. Impaired fat storage rather than altered glucose
metabolism in adipocytes probably contributes to development
of insulin resistance in muscle and other tissues, in particular
via increased delivery of nonesterified fatty acids into circulation.
Lipid metabolism of adipose tissue is affected by the energy
status of fat cells.
In vitro experiments indicated the dependence
of both lipogenesis and lipolysis on ATP levels in adipocytes.
Thus, respiratory uncoupling in adipocytes that results in stimulation
of energy dissipation and depression of ATP synthesis may contribute
to the control of lipid metabolism, adiposity, and insulin sensitivity.
This notion is supported by the expression of UCPs in adipocytes,
for example, UCP2, UCP5, as well as some protonophoric anion
transporters, and by induction of UCP1 and UCP3 in white fat
by pharmacological treatments that reduce adiposity. A negative
correlation between expression of UCPs in adipocytes and accumulation
of white fat was also found. Expression of UCP1 from the adipose-specific
promoter in the aP2-
Ucp1 transgenic mice mitigated obesity induced
by genetic or dietary factors. The obesity resistance, accompanied
by respiratory uncoupling in adipocytes and increased energy
expenditure, resulted from ectopic expression of UCP1 in white,
but not brown fat. Probably due to depression of the ATP/ADP
ratio, both fatty acid synthesis and lipolytic action of norepinephrine
in adipocytes of transgenic mice were relatively low. Expression
of regulatory G-proteins, which are essential for both catecholamine
and insulin signaling in adipocytes, was also altered by ectopic
UCP1. These results support the role of protonophoric proteins
in adipocytes in the control of adiposity and insulin sensitivity.
Antidiabetic effects of thiazolidinediones, fibrates, ß
3-adrenoreceptor
agonists, dietary n-3 PUFAs, and leptin may be explained at
least partially by their effects on the energy and hence also
the lipid metabolism of fat cells.
PRA
ÁK
, Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague, Czech Republic. Voice: (+420-2) 4106 2554; fax: (+420-2) 4106 2599. 
