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Obesity is associated with an increased incidence of high-grade prostate cancer and poor prognosis for prostate cancer patients. Recently, we showed that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by crown-like structures (CLS) consisting of dead or dying adipocytes surrounded by macrophages, was associated with high-grade prostate cancer. It is possible, therefore, that agents that suppress periprostatic WAT inflammation will alter the development or progression of prostate cancer. Pioglitazone, a ligand of PPARγ, is used to treat diabetes and possesses anti-inflammatory properties. Here, our main objectives were to determine whether pioglitazone inhibited obesity-related periprostatic WAT inflammation in mice and then to elucidate the underlying mechanism. Treatment with pioglitazone reduced the density of CLS in periprostatic fat and suppressed levels of …