Figure 6. Pioglitazone induces AdipoR2.

A, At 6 weeks of age, C57BL/6J male mice were fed either low fat (LF) diet or high fat (HF) diet. The LF diet fed mice were randomized to one of two groups. One group was sacrificed at 18 weeks of age after 12 weeks on LF diet while the second group was sacrificed at 26 weeks of age after 20 weeks on LF diet. The other mice were fed HF diet for 12 weeks to induce obesity and then randomized to one of four groups. One group was sacrificed at 18 weeks of age after 12 weeks on HF diet. The second group was continued on HF diet, the third group was switched to HF diet containing 0.006% w/w pioglitazone and the fourth group was switched to HF diet containing 0.06% w/w pioglitazone for an additional 8 weeks until sacrifice at 26 weeks of age. AdipoR2 mRNA levels were quantified in periprostatic white adipose tissue. B, 3T3-L1 adipocytes were treated with 0–2.5 µM pioglitazone for 6 hours. Relative AdipoR2 expression was quantified. C, 3T3-L1 adipocytes were pretreated with 0–2.5 µM pioglitazone for 6 hours. Subsequently, cells were treated with TNF-α for an additional 6 hours. Relative AdipoR2 expression was quantified. D, 3T3-L1 adipocytes were transfected with control or AdipoR2 siRNA and levels of AdipoR2 were quantified. E, 3T3-L1 adipocytes were transfected with control siRNA or AdipoR2 siRNA. Seventy-two hours after transfection, cells were treated with vehicle or pioglitazone for 6 hours. Subsequently, cells received TNF-α (10 ng/mL) for an additional 6 hours. Levels of MCP-1 mRNA were quantified. For A–E, mean ± SD (error bars) are shown. A, n=3–7/group; *p<0.05, **p<0.01 compared to mice fed with LF diet for 20 weeks. B–E, n=4–6/group; *p<0.05, **p<0.01, ***p<0.001; F, high fat diet feeding causes periprostatic adipocyte hypertrophy and increased production of MCP-1. MCP-1 is a chemokine that is important for recruitment of blood monocytes into periprostatic adipose tissue where they undergo differentiation and become macrophages leading to the formation of crown-like structures (CLS). Pioglitazone induces adiponectin and its receptor (AdipoR2) which act, in turn, to block MCP-1 expression leading to a reduction in CLS.