Roles of PPARγ in the adipocyte. In this model, PPARγ acts at two steps to regulate adipocyte size and insulin sensitivity. First, PPARγ promotes the differentiation of pre-adipocytes (P) to normal, insulin-sensitive, small adipocytes (S), a step that can be activated by providing artificial PPARγ agonists, the thiazolidinediones (TZD). PPARγ also plays a critical role in adipocyte hypertrophy and development of insulin resistance under a high-fat diet. In wild-type mice, such a diet promotes adipocyte hypertrophy, which converts small adipocytes (S) into large adipocytes (L). These latter cells, in turn, induce factors such as TNF-α and FFAs, which promote insulin resistance. PPARγ+/– animals therefore enjoy some protection from adipocyte hypertrophy and the development of insulin resistance under a high-fat diet. Adapted from ref. 38.