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J Biol Chem, Vol. 274, Issue 35, 24965-24972, August 27, 1999
From the Extracellular factors and intracellular signaling
pathways involved in early events of adipocyte differentiation are
poorly defined. It is shown herein that expression of leukemia
inhibitory factor (LIF) and LIF receptor is developmentally regulated
during adipocyte differentiation. Preadipocytes secrete bioactive LIF, and an antagonist of LIF receptor inhibits adipogenesis. Genetically modified embryonic stem (ES) cells combined with culture conditions to
commit stem cells into the adipocyte lineage were used to examine the
requirement of LIF receptor during in vitro development of adipose cells. The capacity of embryoid bodies derived from
lifr
Leukemia Inhibitory Factor and Its Receptor Promote Adipocyte
Differentiation via the Mitogen-activated Protein Kinase Cascade
,,,,,,,, and
Centre de Biochimie (IFR349 and UMR6543
CNRS) Université de Nice-Sophia Antipolis, Faculté des
Sciences, Parc Valrose, 06108 Nice, France, the § Centre
for Genome Research, University of Edinburgh, Edinburgh,
EHG3JQ Scotland, United Kingdom, and the ¶ School of Life and
Health Sciences, Aston University,
Birmingham B47HET, United Kingdom
/ ES cells to undergo adipocyte
differentiation is dramatically reduced. LIF addition stimulates
adipocyte differentiation of Ob1771 and 3T3-F442A preadipocytes and
that of peroxisome proliferator-activated receptor 
2 ligand-treated
mouse embryonic fibroblasts. Expression of the early adipogenic
transcription factors C/EBP
and C/EBP
is rapidly stimulated
following exposure of preadipose cells to LIF. The selective inhibitors
of mitogen-activated protein kinase kinase, i.e. PD98059
and U0126, inhibit LIF-induced C/EBP gene expression and prevent
adipocyte differentiation induced by LIF. These results are in favor of
a model that implicates stimulation of LIF receptor in the commitment
of preadipocytes to undergo terminal differentiation by controlling the
early expression of C/EBP and C/EBP genes
via the mitogen-activated protein kinase cascade.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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