12
Adipocytes
Fig. 3
Fluorescence micrograph of a cultured adipocyte expressing EGFP–perilipin
fusion protein. A C3H 10T1/2 mesenchymal cell was differentiated in culture and
transfected with an expression vector encoding perilipin fused to enhanced green
fluorescent protein. Note the localization of the fluorescence to surface of the numerous
lipid droplets (see color plate p. xxi).
a key role in the terminal differentiation
of adipocytes (discussed in more detail be-
low). The importance of C/EBP
β
and
δ
for adipogenesis was clearly demonstrated
by loss-of-function and gain-of-function
genetic studies in mice. Overexpression
of either C/EBP
β
or
δ
in preadipocytes
enhanced adipogenesis, while embryonic
Fbroblast cells derived from mice lacking
either C/EBP
β
or
δ
had reduced levels of
adipogenesis compared with wild type.
The induction of C/EBP
β
and
δ
is
immediately followed by an increase in
PPAR
γ
and C/EBP
α
expression. PPAR
γ
is a member of the nuclear hormone
receptor family of ligand-activated tran-
scription factors. It is absolutely required
for adipocyte differentiation, as a genetic
knockout of the PPAR
γ
gene in mice pre-
vents the development of all fat tissue.
In addition to its crucial role in adipocyte
differentiation PPAR
γ
is the receptor for
the thiazolidinedione (TZD) class of an-
tidiabetic drugs, indicating that it is also
important in metabolic regulation in adult
organisms. In mice and humans there
are two isoforms, PPAR
γ
1 and PPAR
γ
2,
which are derived from the same gene by
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