Figure 9.

Chronic treatment of mice with IKKβ inhibitor ameliorates diet-induced obesity. (A and B) 8-wk-old male C57BL/6 mice were fed a WD and treated with vehicle or 10 mg/kg body weight of BMS-345541 by daily oral gavage for 8 wk. Body weight (A) was measured weekly and fat and lean mass (B) were measured at the end of feeding study (n = 11–12 mice). (C) Representative photographs of subcutaneous (Sub) and epididymal (Epi) WAT. (D) Expression of Smurf2 and other NF-κB target genes in WAT were analyzed by QPCR (n = 4 mice). (E) Western blot analysis of nuclear β-catenin levels in WAT of control or BMS-345541-treated mice. Nuclear proteins were probed with anti-Histone H3 antibodies an internal control. (F) Oil red O staining of adipose SV cells from control or BMS-345541–treated mice induced by differentiation medium. (G) Adipose SV cells isolated from control or BMS-345541-treated mice were incubated with vehicle or 100 nM PS-341 as indicated for 4 h. β-catenin was immunoprecipitated with anti–β-catenin antibodies and then probed with antiubiquitin monoclonal antibodies. The whole cell lysates were probed with anti–β-catenin antibodies as an internal control. Similar results were obtained from at least three independent experiments. All data are mean ± SD. *, P < 0.05; **, P < 0.01. Bars: (F, bottom) 100 µm.