TITLE:
Role of sphingosine kinases and sphingosine 1-phosphate in mediating adipogenesis
AUTHORS:
Lucy D. Mastrandrea
KEYWORDS:
Adipocyte; Adipogenesis; Obesity; Sphingosine Kinase; 3T3-L1 Cells; Sphingosine 1-Phosphate; Sphingosine 1-Phosphate Receptor
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.3 No.2,
May
15,
2013
ABSTRACT: Recent Background:
Development of obesity involves promotion of preadipocyte differrentiation. This
study investigated the role that sphingosine kinases (SPHK) and ceramide-derived
sphingosine 1-phosphate (S1P) play in adipocyte terminal differentiation. Materials
and Methods: The mouse 3T3-L1 cell line was used as a model for adipogenesis.
Cells were harvested at specific time points after initation of differentiation,
and SPHK activity was measured. 3T3-L1 cells were treated with S1P and
expression of early adipogenesis transcription markers was measured by real
time PCR. The expression of S1P-receptors (S1PRs) during differentiation was
measured. Results: SPHK activity is induced when 3T3-L1 cells are treated
with insulin, dexamethasone, and isobutylmethylxanthine to induce
differentiation. SPHK1 is active in preadipocytes and early in the
differentiation process. Both SPHK1 and SPHK2 isozymes contribute to activity
in differentiated adipocytes. Inhibition of SPHK1 attenuates adipocyte differentiation; however, extracellular S1P does not rescue the effect of SPHK1
inhibition on adipogenesis. Although treatment of preadipocytes with S1P
induced message expression of the early adipogenesis transcription factor CC AAT/
binding proteinalpha, continued treatment did not fully support the
development of differentiated adipocytes. Sphingosine 1-phosphate receptors
(S1PRs) are expressed in preadipocytes and message expression declines markedly
during adipocyte differentiation. Conclusion: These results demonstrate that
the contribution of SPHK and S1P to adipogenesis is mediated primarily
through biphasic activation of SPHK1 and 2 with extracellular S1P and S1PRs
playing little role during preadipocyte differentiation.