Interferon-gamma (IFNgamma) has been shown to decrease the expression and activity of lipoprotein lipase (LPL). Hence, we searched for IFNgamma sensitive binding sites within the murine LPL promoter. A region of the LPL promoter was identified that specifically binds nuclear, but not cytosolic, extracts isolated from IFNgamma-treated 3T3-L1 adipocytes. EMSA analysis revealed that two protein complexes bind to this site within the LPL promoter and supershift analysis demonstrated that both of these complexes contained STAT1 proteins. In addition, we have shown that this effect is specific for IFNgamma, since LIF treatment, which also induces STAT1, did not confer binding to this site. Interestingly, binding to this site within the LPL promoter could be effectively competed with a STAT1 binding site that we previously identified in the PPARgamma2 promoter. Also, IFNgamma treatment resulted in decreased levels of LPL protein. In summary, we have identified a STAT I binding site within the murine LPL promoter which likely plays a role in the IFNgamma induced decrease of LPL expression. (C) 2003 Elsevier Inc. All rights reserved.