Effects of Pioglitazone on Survival and Omental Adipocyte Function in Mice with Sepsis Induced by Cecal Ligation and Puncture

Abstract

To examine the effects of pioglitazone, peroxisome proliferator-activated receptor-gamma (PPAR-γ), on mortality and omental adipocyte function in mice with cecal ligation and puncture (CLP). Male mice were assigned to receive (1) vehicle/sham-operation, (2) pioglitazone/CLP, or (3) vehicle/CLP. Pioglitazone was injected intraperitoneally for 7 d before operation. Serum and omental tissue were collected before, 24, and 48 h after CLP. Serum levels of adiponectin, cytokine, and chemokine were measured with ELISA. mRNA expressions in omental tissues were determined by RT-PCR. Survival was monitored for 7 d after CLP. Survival after CLP was significantly better in the pioglitazone/CLP than in the vehicle/CLP. Serum adiponectin levels before CLP were higher in the pioglitazone/CLP than in the vehicle/CLP. Treatment with pioglitazone significantly inhibited the increases in the serum interleukin-6 and monocyte chemoattractant protein-1 (MCP-1) levels after CLP and lowered the mRNA expressions of proinflammatory cytokines, interleukin-6, and MCP-1 in omental tissue after CLP. The anti-inflammatory effects of pioglitazone on omental adipocyte function appear to be mediated in part by PPAR-γ activation, which down-regulates the production of inflammatory mediators.