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Adipocytes are highly specialized cells that play a major role in energy homeostasis in vertebrate organisms. Obesity is the primary disease of fat cells and a major risk factor for the development of non-insulin dependent diabetes mellitus (NIDDM), cardiovascular disease, and hypertension. Obesity and its related disorders results in dysregulation of the mechanisms that control the expression of a wide variety of genes in adipocytes. Significant advances towards an understanding of these regulatory processes have been made by the identification of transcription factors that regulate the differentiation of fat cells and are involved in the induction and maintenance of adipocyte gene expression.
Our research has focused on the STAT family of transcription factors and on PPARγ, a member of the nuclear hormone superfamily. STATs comprise a family of latent transcription factors that upon activation by a variety of stimuli will translocate to the nucleus. STATs can be rapidly activated to regulate gene expression and represent a relatively unexplored paradigm in the transcriptional regulation of fat cells. Our PPARγ studies have focused on how covalent modifications of this protein modulate its transcriptional activity
Our recent studies demonstrate that STAT 5A can promote adipogenesis in non-precursor cells. In addition, we have shown that STAT 5A interacts with glucocorticoid receptor (GR) and the association of these two transcription factors is regulated during adipogenesis. We have also identified some STAT target genes in adipocytes, including fatty acid synthase. Our studies will hopefully lead to insights into the molecular mechanisms regulating energy homeostasis and may contribute to understanding the defects underlying obesity and NIDDM.
Floyd, Z.E. and Stephens, J. M. (2004) Control of PPARγ2 stability and transcriptional activity by SUMOylation. Obesity Research, 6, 921-928.
Hogan, J.C. and Stephens, J.M. (2005) Effects of Leukemia Inhibitor factor (LIF) on 3T3-L1 adipocytes. Journal of Endocrinology 185, 485-496.
Zvonic, S., Baugh J.E. Jr., Arbour-Reily, P., Mynatt, R.L. and Stephens, J.M. (2005) Cross-talk among gp130 cytokines in adipocytes. J. Biol. Chem. 280, 33856-33863.
Hogan, J.C. and Stephens, J.M. (2005) The regulation of fatty acid synthase (FAS) by STAT5A. Diabetes 54, 1968-1975.
Stephens, J.M. and Vidal-Puig, A. (2006) An update on Visfatin/PBEF, an ubiquitously expressed, illusive cytokine that is regulated in obesity. Current Opinion in Lipidology 17, 128-131.
He, F., and Stephens, J.M. (2006) Induction of SOCS-3 is insufficient to confer IRS-1 protein degradation in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 344, 95-98.