Cyclin-dependent Kinase Inhibitor, p21 WAF1/CIP1 , Is Involved in Adipocyte Differentiation and Hypertrophy, Linking to

mice fed high energy diets had reduced adipose tissuemass and adipocyte size accompanied by a marked improve-ment in insulin sensitivity. Knockdown of p21 in enlarged epi-didymal fat of diet-induced obese mice and also in fully differ-entiated 3T3-L1 adipocytes caused vigorous apoptosis byactivatingp53.Thus,p21isinvolvedinbothadipocytedifferen-tiationandinprotectinghypertrophiedadipocytesagainstapo-ptosis. Via both of these mechanisms, p21 promotes adiposetissue expansion during high fat diet feeding, leading toincreased downstream pathophysiological consequences suchas insulin resistance.