Loss of cyclin-dependent kinase inhibitors produces adipocyte hyperplasia and obesity

SPECIFIC AIMThe cell cycle inhibitors p27 and p21 play a role in adipocyte differentiation in vitro and might be important factors in the determination of adipocyte number in vivo. The aim of this research was to determine the effect of these cell cycle inhibitors on adipose tissue by using animals lacking one or both of these proteins. To examine this, we compared adipose development and metabolic parameters in p27 and p21 knockouts (p27KO and p21KO, respectively), p27/p21 double knockout (DBKO) and wild-type (WT) mice.PRINCIPAL FINDINGS1. Mice lacking p27 and/or p21 show temporal differences in body weight and adipose depotsBody weights of single KO mice were not initially different from WT, but DBKO weights were heavier than WT by 45 days of age. From days 60–120, both p27KOs and p21KOs were heavier than WT mice and DBKO mice were heavier than all other groups. By day 120, DBKO mice weighed 100% more than WT. At 120 days of age, DEXA analysis indicated that adipose mass in DBKO mice was increased 670% ...