['The etiology of some obesity may involve adipocyte hyperplasia. However, the role of adipocyte number in establishing adipose mass is unclear. Cyclin-dependent kinase inhibitor p27 regulates activity of cyclin/cyclin-dependent kinase complexes responsible for cell cycle progression. This protein is critical for establishing adult adipocyte number, and p27 knockout increases adult adipocyte number. The SCF (for Skp1-Cullin-F-box protein) complex targets proteins such as p27 for ubiquitin-proteosome degradation; the F box protein S phase kinase-associated protein 2 (Skp2), a component of the SCF complex, specifically recognizes p27 for degradation. We used Skp2 knockout (Skp2(-/-)) mice to test whether Skp2 loss decreased adipose mass and adipocyte number.', 'We measured body weight, adipose mass, adipocyte diameter and number, and glucose tolerance in wild-type (WT), Skp2(-/-), and p27(-/-)Skp2(-/-) mice. Mouse embryo fibroblasts (MEFs) from WT and Skp2(-/-) fetuses were differentiated to determine whether Skp2 directly affected adipogenesis.', 'Skp2(-/-) mice had a 50% decrease in both subcutaneous and visceral fat pad mass and adipocyte number; these decreases exceeded those in body weight, kidney, or muscle. To test the hypothesis that Skp2 effects on adipocyte number involved p27 accumulation, we used p27(-/-)Skp2(-/-) double knockout mice. The Skp2(-/-) decrements in adipocyte number and fat pad mass were totally reversed in p27(-/-)Skp2(-/-) mice. Adipogenesis was inhibited in MEFs from Skp2(-/-) vs. WT mice, and this inhibition was absent in MEFs from p27(-/-)Skp2(-/-) mice.'] Does the F box protein S phase kinase-associated protein 2 regulate adipose mass and adipocyte number in vivo?